2-substituted-2-cyclopentenones

ABSTRACT

2-Substituted-2-cyclopentenones represented by the formula (I): ##STR1## wherein A is a hydroxyl group or ##STR2## and B is a hydrogen atom or A and B are bonded together to form one bonding arm; 
     R 1  represents a substituted or unsubstituted hydrocarbon group having 1 to 10 carbon atoms; 
     R 2  represents a substituted or unsubstituted aliphatic hydrocarbon group having 1 to 10 carbon atoms; 
     R 3  represents a substituted or unsubstituted aliphatic hydrocarbon group having 1 to 10 carbon atoms; wherein, 
     when R 3  is a single bond bonded to the cyclopentene skeleton, X represents a hydrogen atom, a hydroxyl group or a protected hydroxyl group; and 
     when R 3  is a double bond bonded to the pentene skeleton, X represents a bonding arm constituting a part of said double bond; and 
     m and n independently represent 0, 1 or 2.

This is a continuation of application Ser. No. 07/340,207, filed Apr.19, 1989 now abandoned.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to novel 2-substituted-2-cyclopentanones.More specifically, the present invention relates to2-substituted-2-cyclopentenones having pharmacological activities suchas an excellent antitumor activity, and an excellent bone formationacceleration activity, and to an anti-tumor agent and a bone formationaccelerator.

2. Description of the Related Art

Prostaglandins are compounds having specific biological activities suchas platelet aggregation inhibitory activities and hypotensiveactivities, and are naturally occurring substances which are useful astherapeutical agents for peripheral circulatory organ system diseases incurrent medical treatments. Among these prostaglandins, prostaglandins Aare known to have a double bond in the cyclopentane ring; for example,prostaglandin A₂ is considered to be a medicament having hypotensiveactivities (see E. J. Corey et al, J. Amer. Chem. Soc., 95, 6831, 1973).

Also, since prostaglandins A inhibit potential DNA synthesis, thepossibility of using prostaglandins A as an antitumor agent has beenreported (see Biochem. Biophys. Res. Commun., 87, 795, 1979; W. A.Turner et al, Prostaglandins and Cancer: First International Conference365-368, 1982.

European Unexamined Published Patent Publication No. 0106576 (publishedon Apr. 25, 1984), disclosed 4,5-substituted 2-cyclopentenones includingprostaglandins A, among which are5-alkylidene-4-substituted-2-cyclopentenones represented by the formula:##STR3## wherein W represents a hydrocarbon group having 1 to 12 carbonatoms which also may be substituted, and Y represents a hydrocarbongroup having 1 to 12 carbon atoms which also may be substituted and5-(1-hydroxyhydrocarbon)-4-substituted-2-cyclopentenones of the formula:##STR4## wherein W' and Y' are the same as W and Y, respectively.Further, it is disclosed that these compounds are useful for thetreatment of malignant tumors.

Also, European Unexamined Published Patent Publication No. 0131441(published on Jan. 16, 1985), disclosed5-alkylidene-2-halo-4-substituted-2-cyclopentenones of the formula:##STR5## wherein Ra represents a substituted or non-substitutedhydrocarbon having 1 to 12 carbon atoms or a substituted ornon-substituted phenyl group; Rb represents a substituted ornon-substituted hydrocarbon having 1 to 12 carbon atoms; and Xrepresents a halogen atom, and further, that these compounds aresimilarly effective for the treatment of malignant tumors.

Further, prostaglandins D and J different from prostaglandins A areknown to be useful as antitumor agents (Japanese Unexamined PatentPublication (Kokai) 58-216155 and proceedings of the National Academy ofSciences of the United States of America (Proc. Natl. Acad. Sci.U.S.A.), 81, 1317-1321, 1984).

Also, prostaglandin analogues represented by the formula: ##STR6## andisolated from coral produced in Okinawa [Okinawa soft coral: clavulariaviridis] are known to have an antiinflammatory activity and antitumoractivity as physiological activities thereof [see Kikuchi et al,Tetrahedron Lett., 23, 5171, 1982; Kobayashi et al, Tetrahedron Lett.,23, 5331, 1982; Masanori Fukushima, Cancer and Chemotherapy, 10, 1930,1983).

Japanese Unexamined Patent Publication (Kokai) No. 59-59646 disclosedculavulon derivatives including the above natural products of theformula: ##STR7## R¹ and R² together represent a keto group, or onethereof is a hydrogen group and the other is hydroxy group, R³ is ahydrogen atom or acetoxy group, n is 0 or 1, n being 0 when there is adouble bond between the positions 8 and 12, a, b, c, d, and e are each 1or 2, and the dotted line denotes a single bond or double bond between cand d, and that these compounds are useful as antiinflammatory agents.

Japanese Unexamined Patent Publication (Kokai) No. 59-184158 disclosed,as a compound having a similar antiinflammatory activity, culavulonderivatives of the formula: ##STR8## wherein Ac denotes an acetyl group.

Japanese Unexamined Patent Publication (Kokai) No. 60-4129 disclosedthat the culavalon derivatives included in the above two formulae areuseful as antitumor agents.

E. J. Corey et al synthesized the culavalon derivatives represented bythe following formula: ##STR9## (Journal of the American ChemicalSociety (J. Am. Chem. Soc.), 106, 3384, 1984).

Nagaoka et al similarly synthesized culavulon derivatives represented bythe following formula: ##STR10## (Tetrahedron Letters, vol. 25, No. 33,pages 3621-3624, 1984).

Further, recently, punaglandins 1 and 2 represented by the formula:##STR11## and the formula: ##STR12## were isolated from Telesto riiseigrowing on a ship's bottom at Oaf island. B. J. Baker, J. of AmericanChem. Soc., 107, 2976, 1985.

Also, published PCT Patent Application No. WO85-03706 (publication date:Aug. 29, 1985) disclosed punaglandins represented by the followingformula: ##STR13## wherein R¹ resents a hydrogen atom, C₁ -C₁₀ an alkylgroup or one equivalent cation, R², R³, R⁴ may be the same or different,and each represents a hydrogen atom or C₂ -C₁₀ acyl group, and therepresentation denotes a single bond or double bond, and that thesepunaglandins are useful for the therapy of malignant tumors.

Masanori Fukushima et al reported that the compounds of the followingformula included in the above formula: ##STR14## have an antitumoractivity (see Masanori Fukushima et al collected abstracts of the 43rdMeeting of Japanese Society of Cancer, p. 258, 1984).

Further, Japanese Unexamined Patent Publication (Kokai) No. 62-96438disclosed 4-hydroxy-2-cyclopentenones which are culavulon analogues andpunaglandin analogues of the formula: ##STR15## wherein X represents ahydrogen atom or a halogen atom; A and B represent a combination of Awhich is a hydrogen atom and B which is a hydroxyl group or A and B arebonded mutually to represent one bonding arm; R¹ represents asubstituted or non-substituted alkyl group, and an alkenyl group oralkynyl group having 1 to 10 carbon atoms; R² represents a substitutedor non-substituted alkyl, alkenyl or alkynyl group having 1 to 10 carbonatoms; and R³ represents a hydrogen atom or a protective group for ahydroxyl group; with the proviso that R² cannot be 2-octenyl,8-acetoxy-2-octenyl or 2,5-octadienyl and that these compounds areuseful for the therapy of malignant tumors.

Furthermore, the bone metabolism of an average healthy human isconsidered to be valid when a good balance is maintained betweenrepeated bone resorption with an osteoclast and bone formation with anosteoblast, and when this balance between bone resorption and boneformation is disturbed, diseases such as osteoporosis or osteomalaciamay occur. As the therapeutical agents for such bone diseases, activetype vitamin preparations, calcitonin preparations, diphosphonic acidpreparations, estrogen preparations, and calcium preparations may beemployed, but although many of these preparations have been reported toinhibit bone resorption, etc., none have clearly manifested an effect ofaccelerating bone formation. Further, the effects of these preparationsare uncertain, and accordingly, there is a strong demand for thedevelopment of a drug which causes an acceleration of bone formationwith osteoblast, without uncertainty about the effects thereof.

Koshihara et al. found that prostaglandin D₂ has a calcificationaccelerating activity on human osteoblast, as reported in theBiochemical Society of Japan (Collected abstracts, p. 767, 1988),thought to be caused by the activity of Δ¹² -prostaglandin J₂ formed bya decomposition of prostaglandin D₂. Nevertheless, a bone accelerationactivity of the 2-substituted-2-cyclopentanones is not known.

SUMMARY OF THE INVENTION

Accordingly, an object of the present invention is to obviate theabove-mentioned problems in the prior art and to provide novel2-substituted-2-cyclopentenones, namely 2-cyclopentenones substituted atthe 2-position with a sulfur atom.

Another object of the present invention is to provide2-substituted-2-cyclopentenones having a remarkable antitumor activity.

A further object of the present invention is to provide2-substituted-2-cyclopentenones having a remarkable bone formationaccelerating activity.

A still further object of the present invention is to provide a processfor producing 2-substituted-2-cyclopentenones of the present invention.

Other objects and advantages of the present invention will be apparentfrom the description set forth hereinbelow.

In accordance with the present invention, there is provided2-substituted-2-cyclopentenones represented by the formula (I):##STR16## wherein A is a hydroxyl group or ##STR17## and B is a hydrogenatom or A and B are bonded together to form one bonding arm;

R¹ represents a substituted or unsubstituted hydrocarbon group having 1to 10 carbon atoms;

R² represents a substituted or unsubstituted aliphatic hydrocarbon grouphaving 1 to 10 carbon atoms;

R³ represents a substituted or unsubstituted aliphatic hydrocarbon grouphaving 1 to 10 carbon atoms; wherein,

when R³ is a single bond bonded to the cyclopentene skeleton, Xrepresents a hydrogen atom, a hydroxyl group or a protected hydroxylgroup; and

when R³ is a double bond bonded to the pentene skeleton, X represents abonding arm constituting a part of said double bond; and

m and n independently represent 0, 1 or 2.

DESCRIPTION OF THE PREFERRED EMBODIMENT

In the above formula (I), A and B represent a combination of A which isa hydroxyl group or ##STR18## and B is a hydrogen atom or A and B arebonded together to represent one bonding arm. That is, when A is ahydroxyl group and B is a hydrogen group, the above formula (I)represents 2-substituted-2-cyclopentenones represented by the followingformula (I-b'): ##STR19## wherein R¹, R², R³, X and n are as definedabove; when A is ##STR20## and B is a hydrogen atom, the above formula(I) represents 2-substituted-2-cyclopentanones represented by thefollowing formula (I-b"): ##STR21## wherein R¹, R², R³, X, m and n areas defined above; when A and B are bonded together to represent onebonding arm, the above formula (I) represents2-substituted-2-cyclopentenones represented by the following formula(I-a): ##STR22## wherein R¹, R², R³, X and n are as defined above, andthe representation denotes that the substituent bonded to the doublebond is in an E-configuration or a Z-configuration or a mixture thereofat any desired ratio.

In the above formula (I), R¹ represents a substituted or non-substitutedhydrocarbon group having 1 to 10 carbon atoms. Examples of thenon-substituted hydrocarbon group having 1 to 10 carbon atoms includealkyl groups such as methyl, ethyl, propyl, isopropyl butyl, isobutyl,s-butyl t-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl,nonyl, decyl and the like; aralkyl groups such as benzyl, phenetyl,phenylpropyl, phenylbutyl and the like; or aryl groups such as phenyl,p-tolyl, 1-naphthyl, 2-naphthyl groups, and the like. The hyarocarbongroup may be substituted with a plural different substitution groups.The substituents on such hydrocarbon groups include a hydroxyl group;tri(C₁ -C₇)hydrocarbonsilyloxy groups such as trimethylsilyloxy,triethylsilyloxy, t-butyldimethylsilyloxy, t-butyldiphenylsilyloxy, andtribenzylsilyloxy groups; halogen atoms such as fluorine, chlorine, andbromine; alkoxy groups such as methoxy and ethoxy groups; acyloxy groupssuch as acetyloxy and propanoyl groups; and acyl groups such as acetyland propionyl groups; alkoxycarbonyl groups such as methoxycarbonyl,ethoxycarbonyl, and propoxycarbonyl; and carboxyl group. Preferably R¹represents alkyl groups having 1 to 5 carbon atoms such as methyl,ethyl, propyl, butyl, and pentyl groups, and phenyl groups, particularlypreferably, a methyl group.

In the above formula (I), m and n are the same or different andrepresent 0, 1 or 2. The substituent ##STR23## represents ahydrocarbonthio group when m or n is 0, a hydrocarbonsulfinyl group whenm or n is 1, and a hydrocarbonsulfonyl group when m or n is 2.

In the above formula (I), R² represents a substituted or non-substitutedaliphatic hydrocarbon group having 1 to 10 carbon atoms. Examples of thenon-substituted aliphatic hydrocarbon group having 1 to 10 carbon atomsinclude alkyl groups such as methyl, ethyl, propyl, isopropyl, butyl,isobutyl, s-butyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl,octyl, 3,7-dimethyloctyl, nonyl or decyl groups; alkenyl groups such asvinyl, 1-propenyl 2-propenyl, 1-butenyl, 1,3-butadienyl, 2-butenyl,1-pentenyl, 2-pentenyl, 1-hexenyl, 2-hexenyl, 1,5-hexadienyl, 3-hexenyl,1-heptenyl, 1-octenyl, 1,7-octadienyl, 1-nonenyl or 1-decenyl groups;and alkynyl groups such as ethynyl, 1-propynyl, 2-propynyl, 1-butynyl,3-buten-1-ynyl, 2-butynyl, 1-pentynyl, 2-pentynyl, 1-hexynyl, 2-hexynyl,5-hexen-1-ynyl, 3-hexynyl, 1-heptynyl, 1-octynyl, 7-octen-1-ynyl,1-nonynyl or 1-decynyl groups. The aliphatic hydrocarbon group may besubstituted with plural different substitution groups. The substitutenton such aliphatic hydrocarbon groups includes --COOR⁵ (wherein R⁵represents a hydrogen atom, an alkyl group having 1 to 10 carbon atomsor one equivalent cation); --OR⁶ (wherein R⁶ represents a hydrogen atom;an acyl group having 2 to 7 carbon atoms; a tri(C₁ -C₇)hydrocarbonsilylgroup; a group which forms an acetal bond together with the oxygen atomto which R⁶ is bonded; an aromatic hydrocarbon group which may besubstituted with a halogen atom, a hydroxyl group, a tri(C₁-C₇)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, analkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms); anaromatic hydrocarbon group which may be substituted with a halogen atom,a hydroxyl group a tri(C₁ -C₇)hydrocarbonsilyloxy group, a carboxylgroup, an acyloxy group having 2 to 7 carbon atoms, an acyl group having2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms,an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1to 4 carbon atoms; or an alicyclic group which may be substituted with ahalogen atom, a hydroxyl group, a tri(C₁ -C₇)hydrocarbonsilyloxy group,a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acylgroup having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5carbon atoms, an alkyl group having 1 to 4 carbon atoms, or an alkoxygroup having 1 to 4 carbon atoms. Examples of R⁵ in --COOR⁵ include ahydrogen atom; alkyl groups having 1 to 10 carbon atoms such as methyl,ethyl, propyl, isopropyl, butyl, s-butyl, t-butyl, pentyl, neopentyl,hexyl, heptyl, octyl, nonyl or decyl groups; one equivalent cation suchas cations of ammonium, tetramethyl ammonium, monomethyl ammonium,dimethyl ammonium, trimethyl ammonium, benzyl ammonium, and phenetylammonium, or a morpholinium cation, piperidinium cation or Na⁺, K⁺,1/2Ca²⁺, 1/2Mg²⁺, 1/2Zn²⁺, 1/3Al³⁺. Preferably, R⁵ represents a hydrogenatom, methyl group, and ethyl group.

Examples of R⁶ in --OR⁶ include a hydrogen atom; acyl groups having 2 to7 carbon atoms such as acetyl, propionyl, butyryl, isobutyryl, valeryl,isovaleryl, hexanoyl, heptanoyl, and benzoyl groups; tri(C₁-C₇)hydrocarbonsilyl groups such as trimethylsilyl, triethylsilyl,t-butyldimethylsilyl, t-butyldiphenylsilyl, and tribenzylsilyl groups;and groups which form an acetal bond together with the oxygen atom towhich R⁶ is bonded such as methoxymethyl, 1-ethoxyethyl,2-methoxy-2-propyl, 2-ethoxy-2-propyl, 2-methoxyethoxymethyl,tetrahydropyran-2-yl, tetrahydrofuran-2-yl, and6,6-dimethyl-3-oxa-2-oxo-bicyclo[3.1.0]-hexan-4-yl groups. Examples ofthe aromatic hydrocarbons which may be substituted with a halogen atom,a hydroxyl group, a tri(C₁ -C₇)hydrocarbonsilyloxy group, a carboxylgroup, an acyloxy group having 2 to 7 carbon atoms, an acyl group having2 to 7 carbon atoms an alkoxycarbonyl group having 2 to 5 carbon atoms,or an alkyl group having 1 to 4 carbon atoms are phenyl, 1-naphthyl,2-naphthyl, and 1-anthranyl. Examples of the substituent are a halogenatom such as fluorine, chlorine, and bromine; a hydroxyl group; tri(C₁-C₇)hydrocarbonsilyloxy groups such as trimethylsilyloxy,triethylsililoxy, t-butyldimethylsilyloxy, t-butyldiphenylsililoxy, andtribenzylsilyloxy groups; a carboxyl group; an acyloxy groups such asacetoxy, propionyloxy, butyryloxy, isobutyryloxy, valeryloxy,isovaleryloxy, hexanoyloxy, heptanoyloxy, and benzoyloxy groups; acylgroups such as acetyl, propionyl, butyryl, isobutyryl, valeryl,isovaleryl, hexanoyl, heptanoyl, and benzoyl groups; alkoxycarbonylgroups such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, ands-butoxycarbonyl groups; alkyl groups such as methyl, ethyl, propyl,isopropyl, butyl, isobutyl, s-butyl, and t-butyl groups; and alkoxygroups such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy,s-butoxy, and t-butoxy groups. Particularly preferably, R⁶ represents ahydrogen atom, acetyl group, trimethylsilyl group, t-butyldimethylsilylgroup, tetrahydropiran-2-yl group, and phenyl group.

Examples of the aromatic hydrocarbon group and the substituent, when thesubstituent group of R² is an aromatic hydrocarbon group which may besubstituted with a halogen atom, a hydroxyl group, tri(C₁-C₇)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, analkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1to 4 carbon atoms, or an alkoxy group having 1 to 4 carbon atoms, arethose as mentioned in the case of R⁶. Preferable substituents arephenyl, 3,4-dimethoxyphenyl, and 4-methoxycarbonylphenyl.

When R² is an alicyclic hydrocarbon group having 4 to 10 carbon atomswhich may be substituted with a halogen atom, a hydroxyl group, tri(C₁-C₇)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, analkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1to 4 carbon atoms, or an alkoxy group having 1 to 4 carbon atoms,examples of such an alicyclic group are cyclobutyl, cyclopentyl,cyclohexyl, 1-cyclohexenyl, 3-cyclohexenyl, 4-cyclohexenyl, cycloheptyl,cyclooctyl, bicyclo[4.4.0]decane-2-yl groups and examples of thesubstituent are halogen atoms such as fluorine, chlorine, and bromine; ahydroxyl group; tri(C₁ -C₇)hydrocarbonsilyloxy groups such astrimethylsililoxy, triethylsililoxy, t-butyldimethylsilyloxy,t-butyldiphenylsililoxy, and tribenzylsilyloxy groups; a carboxyl group;acyloxy groups such as acetoxy, propionyloxy, butyryloxy, isobutyryloxy,valeryloxy, isovaleryloxy, hexanoyloxy, heptanoyloxy, and benzoyloxygroups; acyl groups such as acetyl, propionyl, butyryl, isobutyryl,valeryl, isovaleryl, hexanoyl, heptanoyl, and benzoyl groups;alkoxycarbonyl groups such as methoxycarbonyl, ethoxycarbonyl,propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl,and s-butoxycarbonyl groups; alkyl groups such as methyl, ethyl, propyl,isopropyl, butyl, isobutyl, s-butyl, t-butyl groups; and alkoxy groupssuch as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy,s-butoxy, and t-butoxy groups. Particularly preferably,4-hydroxycyclohexyl, 3,5-diacetoxycyclohexyl, cyclopentyl, and3-ethylcyclopentyl can be exemplified.

In the above formula (I), R³ represents a substituted or non-substitutedaliphatic hydrocarbon group having 1 to 10 carbon atoms, and when R³ isbonded through a single bond to the cyclopentene skeleton, X representsa hydrogen atom, a hydroxyl group or a protected hydroxyl group, andwhen R³ is bonded through a double bond to the cyclopentene skeleton, Xrepresents a part of said double bond. More specifically, when R³ isbonded through a single bond to the cyclopentene skeleton, the aboveformula (I) represents 2-substituted-2-cyclopentenones represented bythe following formula (I'): ##STR24## wherein A, B, R¹, R² and n are asdefined above; R³⁴ represents a substituted or non-substituted aliphatichydrocarbon group having 1 to 10 carbon atoms; X¹ represents a hydrogenatom, hydroxyl group or a protected hydroxyl group]; when R³ is bondedthrough a double bond to the cyclopentene skeleton and X represents abond in said double bond, the above formula (I) represents2-substituted-2-cyclopentenones represented by the following formula(I"): ##STR25## wherein A, B, R¹, R², n and the representation are asdefined above; R³³ represents a hydrogen atom or a substituted ornon-substituted aliphatic hydrocarbon group having 1 to 9 carbon atoms.

R³⁴ in the above formula (I') represents a substituted ornon-substituted aliphatic hydrocarbon group having 1 to 10 carbon atoms,and examples of such R³⁴ include the same groups as mentioned above forR², also including the substituents.

X¹ in the above formula (I') represents a hydrogen atom, hydroxyl groupor a protected hydroxyl group, and examples of the protected hydroxylgroup include alkoxy groups such as methoxy, ethoxy, propoxy, andisopropoxy; tri(C₁ -C₇)hydrocarbonsilyloxy groups such astrimethylsilyloxy, triethylsilyloxy, t-butyldimethylsilyloxy,t-butyldiphenylsilyloxy, and tribenzylsilyloxy groups; acetal groupssuch as methoxymethoxy, 1-ethoxyethoxy, 2-methoxyethoxymethoxy, andtetrahydropyran-2-yloxy groups; and acyloxy groups such as acetoxy,propionyloxy, and butyryloxy groups. Preferably, X¹ represents ahydrogen atom, hydroxyl group, methoxy group, ethoxy group,trimethylsilyloxy group, and acetoxy group.

R³³ in the above formula (I") represents a substituted ornon-substituted aliphatic hydrocarbon group having 1 to 9 carbon atomsand examples of the substituent for such R³³ include the samesubstituents as mentioned above for R². Examples of the non-substitutedaliphatic hydrocarbon group having 1 to 9 carbon atoms of R³³ includealkyl groups such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl,s-butyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl ornonyl groups; alkenyl groups such as vinyl, 1-propenyl, 2-propenyl,1-butenyl, 1,3-butadienyl, 2-butenyl, 1-pentenyl, 2-pentenyl, 1-hexenyl,2-hexenyl, 1,5-hexadienyl, 3-hexenyl, 1-heptenyl, 2,6-dimethylheptenyl,1-octenyl, 1,7-octadienyl or 1-nonenyl groups; and alkynyl groups suchas ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 3-buten-1-ynyl,2-butynyl, 1-pentynyl, 2-pentynyl, 1-hexynyl, 2-hexynyl, 5-hexen-1-ynyl,3-hexynyl, 1-heptynyl, 1-octynyl, 7-octen-1-ynyl or 1-nonynyl groups.

Examples of 2-substituted-2-cyclopentenones of the present inventionrepresented by the above-mentioned formula (I) include the compounds setforth below.

(1)2-methylthio-5-(1-hydroxy-6-methoxycarbonylhexyl)-4-(3-t-butyldimethylsilyloxy-1-octenyl)-2-cyclopentenone

(2)2-methylthio-5-(1-hydroxy-6-methoxycarbonyl)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone

(3)2-methylsulfinyl-5-(1-hydroxy-6-methoxycarbonyl-hexyl)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone

(4)2-methylsulfonyl-5-(1-hydroxy-6-methoxycarbonylhexyl)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone

(5)2-methylthio-5-(1-hydroxy-6-carboxyhexyl)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone

(6)2-methylthio-5-(6-methoxycarbonylhexylidene)-4-(3-t-butyldimethylsilyloxy-1-octenyl)-2-cyclopentenone

(7)2-methylthio-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone

(8)2-methylsulfinyl-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone

(9)2-methylsulfonyl-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone

(10)2-methylthio-5-(6-methoxycarbonylhexylidene)-4-(3-actetoxy-1-octenyl)-)-2-cyclopentenone

(11)2-methylthio-5-(6-carboxyhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone

(12)2-methylthio-5-(6-methoxycarbonylhexylidene)-4-(1-octenyl)-2-cyclopentenone

(13)2-methylsulfinyl-5-(6-methoxycarbonylhexylidene)-4-(1-octenyl)-2-cyclopentenone

(14)2-methylsulfonyl-5-(6-methoxycarbonylhexylidene)-4-(1-octenyl)-2-cyclopentenone

(15) 2-methylthio-5-(6-carboxyhexylidene)-4-(1-octenyl)-2-cyclopentenone

(16)2-methylthio-5-(1-methylthio-6-methoxycarbonylhexylidene)-4-(1-octenyl)-2-cyclopentenone

(17)2-methylsulfinyl-5-(1-methylsulfinyl-6-methoxycarbonylhexylidene)-4-(1-octenyl)-2-cyclopentenone

(18)2-methylsulfonyl-5-(1-methylsulfonyl-6-methoxycarbonylhexylidene)-4-(1-octenyl)-2-cyclopentenone

(19)2-ethylthio-5-(1-hydroxy-6-methoxycarbonynlhexyl)-4-(3-t-butyldimethylsililoxy-1-octenyl)-2-cyclopentenone

(20)2-ethylthio-5-(6-methoxycarbonylhexylidene)-4-(3-t-butyldimethylsilyloxy-1-octenyl)-2-cyclopentenone

(21)2-ethylthio-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone

(22)2-ethylsulfinyl-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone

(23)2-ethylsulfonyl-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone

(24)2-ethylthio-5-(6-carboxylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone

(25)2-phenylthio-5-(8-ethoxycarbonyloctylidene)-4-[3-(tetrahydropyran-2-yloxy)-1-octenyl]-2-cyclopentenone

(26)2-phenylthio-5-(8-ethoxycarbonyloctylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone

(27)2-phenylsulfinyl-5-(8-ethoxycarbonyloctylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone

(28)2-phenylsulfonyl-5-(8-ethoxycarbonyloctylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone

(29)2-phenylthio-5-(8-carboxyoctylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone

(30)2-(5-methoxycarbonylpentylthio)-5-(1-hydroxy-6-methoxycarbonyl-2-hexynyl)-4-(3-t-butyldimethylsilyloxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone

(31)2-(5-methoxycarbonylpentylthio)-5-(1-hydroxy-6-methoxycarbonyl-2-hexynyl)-4-(3-hydroxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone

(32)2-(5-methoxycarbonylpentylthio)-5-(6-methoxycarbonyl-2-hexynylidene)-4-(3-t-butyldimethylsilyloxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone

(33)2-(5-methoxycarbonylpentylthio)-5-(6-methoxycarbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone

(34)2-(5-methoxycarbonylpentylsulfinyl)-5-(6-methoxycarbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone

(35)2-(5-methoxycarbonylpentylsulfonyl)-5-(6-methoxycarbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone

(36)2-(3-phenylpropylthio)-5-(1-hydroxy-6-methoxycarbonyl-2-hexynyl)-4-(3-t-butyldimethylsilyloxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone

(37)2-(3-phenylpropylthio)-5-(1-hydroxy-6-methoxycarbonyl-2-hexynyl)-4-(3-t-butyldimethylsilyloxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone

(38)2-(3-phenylpropylthio)-5-(6-methoxycarbonyl-2-hexynylidene)-4-(3-t-butyldimethylsilyloxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone

(39)2-(3-phenylpropylthio)-5-(6-methoxycarbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone

(40)2-(3-phenylpropylsulfinyl)-5-(6-methoxycarbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone

(41)2-(3-phenylpropylsulfonyl)-5-(6-methoxycarbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone

(42)2-phenylthio-5-(1-hydroxy-6-methoxycarbonyl-2-hexynyl)-4-(3-hydroxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone

(43)2-phenylthio-5-(6-methoxycarbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone

(44)2-phenylsulfinyl-5-(6-methoxycarbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone

(45)2-phenylsulfonyl-5-(6-methoxycarbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone

(46)2-(6-methoxylnaphthyl-2-thio)-5-(1-hydroxy-6-methoxycarbonyl-2-hexynyl)-4-(3-hydroxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone

(47)2-(6-methoxynaphthyl-2-thio)-5-(6-methoxycarbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone

(48)2-(6-methoxynaphthyl-2-sulfinyl)-5-(6-methoxycarbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclopentyl-1-propenyl)-2cyclopentenone

(49)2-(6-methoxynaphthyl-2-sulfonyl)-5-(6-methoxycarbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone

(50)2-(4-chlorophenylmethylthio)-5-(1-hydroxy-6-methoxycarbonyl-5-hexenyl)-4-(3-hydroxy-5-methyl-1-nonenyl)-2-cyclopentenone.

(51)2-(4-chlorophenylmethylthio)-5-(6-methoxycarbonyl-5-hexenylidene-4-(3-hydroxy-5-methyl-1-nonenyl)-2-cyclopentenone

(52)2-(4-chlorophenylmethylsulfinyl)-5-(6-methoxycarbonyl-5-hexenylidene)-4-(3-hydroxy-5-methyl-1-nonenyl)-2-cyclopentenone

(53)2-(4-chlorophenylmethylsulfonyl)-5-(6-methoxycarbonyl-5-hexenylidene)-4-(3-hydroxy-5-methyl-1-nonenyl)-2-cyclopentenone

(54)2-ethylthio-5-(1-hydroxy-6-methoxy(carbonylhexyl)-4-[3-(tetrahydropyran-2-yloxy)-3-cyclohexyl-1-propenyl]-2-cyclopentenone

(55)2-ethylthio-5-(6-methoxycarbonylhexylidene)-4-[3-(tetrahydropyran-2-yloxy)-3-cyclohexyl-1-propenyl]-2-cyclopentenone

(56)2-ethylthio-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-3-cyclohexyl-1-propenyl)-2-cyclopentenone

(57)2-(4-methylphenylthio)-5-(1-hydroxy-3-phenyl-2-propenyl)-4-butyl-2-cyclopentenone

(58)2-(4-methylphenylthio)-5-(3-phenyl-2-propenylidene)-4-butyl-2-cyclopentenone

(59)2-(4-methylphenylsulfinyl)-5-(3-phenyl-2-propenylidene)-4-butyl-2-cyclopentenone

(60)2-(4-methylphenylsulfonyl)-5-(3-phenyl-2-propenylidene)-4-butyl-2-cyclopentenone

(61)2-methylthio-5-(1,4,7-trihydroxy-2-heptenyl)-4-(4-phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenone

(62)2-methylthio-5-(1,4,7-trihydroxy-2-heptenyl)-4-(4-phenoxybutyl)-4-hydroxy-2-cyclopentenone

(63)2-methylsulfinyl-5-(1,4,7-trihydroxy-2-heptenyl)-4-(4-phenoxybutyl)-4-hydroxy-2-cyclopentenone

(64)2-methylsulfonyl-5-(1,4,7-trihydroxy-2-heptenyl)-4-(4-phenoxybutyl)-4-hydroxy-2-cyclopentenone

(65)2-methylthio-5-(1-hydroxy-4,7-diacetoxy-2-heptenyl)-4-(4-phenoxybutyl)-4-hydroxy-2-cyclopentenone

(66)2-methylthio-5-(4,7-dihydroxy-2-heptenylidene)-4-(4-phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenone

(67)2-methylthio-5-(4,7-dihydroxy-2-heptenylidene)-4-(4-phenoxybutyl)-4-methoxy-2-cyclopentenone

(68)2-methylthio-5-(4,7-dihydroxy-2-heptenylidene)-4-(4-phenoxybutyl)-4-ethoxy-2-cyclopentenone

(69)2-methylthio-5-(4,7-diacetoxy-2-heptenylidene)-4-(4-phenoxybutyl)-4-hydroxy-2-cyclopentenone

(70)2-methylthio-5-(4,7-diacetoxy-2-heptenylidene)-4-(4-phenoxybutyl)-4-acetoxy-2-cyclopentenone

(71)2-methylsulfinyl-5-(4,7-dihydroxy-2-heptenylidene)-4-(4-phenoxybutyl)-4-hydroxy-2-cyclopetenone

(72)2-methylsulfonyl-5-(4,7-dihydroxy-2-heptenylidene)-4-(4-phenoxybutyl)-4-hydroxy-2-cyclopentenone

(73)2-methylthio-5-(4,7-dihydroxy-2-heptenylidene)-4-(4-phenoxybutylidene)-2-cyclopentenone

(74)2-methylsulfinyl-5-(4,7-dihydroxy-2-heptenylidene)-4-(4-phenoxybutylidene)-2-cyclopentenone

(75)2-methylsulfonyl-5-(4,7-dihydroxy-2-heptenylidene)-4-(4-phenoxybutylidene)-2-cyclopentenone

(76)2-methylthio-5-[1-hydroxy-3-(4-methoxycarbonylcyclohexyl)propyl]-4-(4-phenoxybutyl)-4-hydroxy-2-cyclopentenone

(77)2-methylthio-5-[3-(4-methoxycarbonylcyclohexyl)propylidene]-4-(4-phenoxybutyl)-4-hydroxy-2-cyclopentenone

(78)2-methylsulfinyl-5-[3-(4-methoxycarbonylcyclohexyl)propylidene]-4-(4-phenoxybutyl)-4-hydroxy-2-cyclopentenone

(79)2-methylsulfonyl-5-[3-(4-methoxycarbonylcyclohexyl)propylidene]-4-(4-phenoxybutyl)-4-hydroxy-2-cyclopentenone

(80)2-methylthio-5-[1-hydroxy-4-(4-methoxyphenyl)butyl]-4-(4-phenoxybutyl)-4-hydroxy-2-cyclopentenone

(81)2-ethylthio-5-[4-(4-methoxyphenyl)butylidene]-4-(4-phenoxybutyl)-4-hydroxy-2-cyclopentenone

(82)2-methylsulfinyl-5-[4-(4-methoxyphenyl)butylidene]-4-(4-phenoxybutyl)-4-hydroxy-2-cyclopentenone

(83)2-methylsulfonyl-5-[4-(4-methoxyphenyl)butylidene]-4-(4-phenoxybutyl)-4-hydroxy-2-cyclopentenone

(84)2-phenylthio-5-(1-hydroxyoctyl)-4-(4-phenoxybutyl)-4-hydroxy-2-cyclopentenone

(85)2-phenylthio-5-octylidene-4-(4-phenoxybutyl)-4-hydroxy-2-cyclopentenone

(86)2-phenylsulfinyl-5-octylidene-4-(4-phenoxybutyl)-4-hydroxy-2-cyclopentenone

(87)2-phenylsulfonyl-5-octylidene-4-(4-phenoxybutyl)-4-hydroxy-2-cyclopentenone

(88)2-methylthio-5-(1-hydroxy-6-methoxycarbonylhexyl)-4-[3-(3,4-dimethoxyphenyl)propyl]-4-hydroxy-2-cyclopentenone

(89)2-methylthio-5-(6-methoxycarbonylhexylidene)-4-[3-(3,4-dimethoxyphenyl)propyl]-4-hydroxy-2-cyclopentenone

(90)2-methylsulfinyl-5-(6-methoxycarbonylhexylidene)-4-[3-(3,4-dimethoxyphenyl)propyl]-4-hydroxy-2-cyclopentenone

(91)2-methylsulfonyl-5-(6-methoxycarbonylhexylidene)-4-[3-(3,4-dimethoxyphenyl)propyl]-4-hydroxy-2-cyclopentenone

(92)2-methylthio-5-(1-hydroxy-6-methoxycarbonylhexyl)-4-(3,7-dimethyloctyl)-4-hydroxy-2-cyclopentenone

(93)2-methylthio-5-(6-methoxycarbonylhexylidene)-4-(3,7-dimethyloctyl)-4-hydroxy-2-cyclopentenone

(94)2-methylsulfinyl-5-(6-methoxycarbonylhexylidene)-4-(3,7-dimethyloctyl)-4-hydroxy-2-cyclopentenone

(95)2-methylsulfonyl-5-(6-methoxycarbonylhexylidene)-4-(3,7-dimethyloctyl)-4-hydroxy-2-cyclopentenone

(96)2-methylthio-5-(1-hydroxy-6-methoxycarbonylhexyl)-4-(1-hexynyl)-4-hydroxy-2-cyclopentenone

(97)2-methylthio-5-(6-methoxycarbonylhexylidene)-4-(1-hexynyl)-4-hydroxy-2-cyclopentenone

(98)2-methylsulfinyl-5-(6-methoxycarbonylhexylidene)-4-(1-hexynyl)-4-hydroxy-2-cyclopentenone

(99)2-methylsulfonyl-5-(6-methoxycarbonylhexylidene)-4-(1-hexynyl)-4-hydroxy-2-cyclopentenone

(100)2-methylthio-5-(1-hydroxy-6-methoxycarbonyl-2-hexynyl)-4-(3-hydroxy-3-cyclohexyl-1-propenyl)-4-hydroxy-2-cyclopentenone

(101)2-methylthio-5-(6-methoxycarbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclohexyl-1-propenyl)-4-hydroxy-2-cyclopentenone

(102)2-methylsulfinyl-5-(6-methoxycarbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclohexyl-1-propenyl)-4-hydroxy-2-cyclopentenone

(103)2-methylsulfonyl-5-(6-methoxycarbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclohexyl-1-propenyl)-4-hydroxy-2-cyclopentenone

(104)2-methylthio-5-(1-hydroxy-6-methoxycarbonylhexyl)-4-methyl-4-hydroxyl-2-cyclopentenone

(105)2-methylthio-5-(6-methoxycarbonylhexylidene)-4-methyl-4-hydroxyl-2-cyclopentenone

(106)2-methylsulfinyl-5-(6-methoxycarbonylhexylidene)-4-methyl-4-hydroxy-2-cyclopentenone

(107)2-methylsulfonyl-5-(6-methoxycarbonylhexylidene)-4-methyl-4-hydroxy-2-cyclopentenone

(108)2-methylthio-5-(1-hydroxy-6-methoxycarbonyl)-4-octyl-4-hydroxy-2-cyclopentenone

(109)2-methylthio-5-(6-methoxycarbonylhexylidene)-4-octyl-4-hydroxy-2-cyclopentenone

(110)2-methylsulfinyl-5-(6-methoxycarbonylhexylidene)-4-octyl-4-hydroxy-2-cyclopentenone

(111)2-methylsulfonyl-5-(6-methoxycarbonylhexylidene)-4-octyl-4-hydroxy-2-cyclopentenone

(112)2-methylthio-5-(6-carboxyhexylidene)-4-octyl-4-hydroxy-2-cyclopentenone

(113)2-(2-phenylethylthio)-5-[1-hydroxy-5-(acetoxymethyl)-6-acetoxyhexyl]-4-(6-nonynyl)-4-hydroxy-2-cyclopentenone

(114)2-(2-phenylethylthio)-5-[5-(acetoxymethyl)-6-acetoxyhexylidene]-4-(6-nonynyl)-4-hydroxy-2-cyclopentenone

(115)2-(2-acetoxyethylthio)-5-(1-hydroxy-10-methoxydecyl)-4-benzyl-4-hydroxy-2-cyclopentenone

(116)2-(2-acetoxyethylthio)-5-(10-methoxydecylidene)-4-benzyl-4-hydroxy-2-cyclopentenone

(117)2-(3-acetylphenylmethylthio)-5-[1-hydroxy-4-(4-chlorophenoxy)butyl]-4-(1-octenyl)-4-hydroxy-2-cyclopentenone

(118)2-(3-acetylphenylmethylthio)-5-[4-(4-chlorophenoxy)butyl]-4-(1-octenyl)-4-hydroxy-2-cyclopentenone

Of the 2-substituted-2-cyclopentenones of the above formula (I),2-substituted-2-cyclopentenones represented by the following formula(I-b-11): ##STR26## wherein R¹, R² and R³⁴ are as defined above, butpreferably R² and R³⁴ are aliphatic hydrocarbon groups having 1 to 10carbon atoms which also have as the substitutent --COOR⁵ (where R⁵represents a hydrogen atom, an alkyl group having 1 to 10 carbon atomsor one equivalent cation); --OR⁶ (where R⁶ is a hydrogen atom; an acylgroup having 2 to 7 carbon atoms; a tri(C₁ -C₇)hydrocarbonsilyl group; agroup which forms an acetal bond together with a oxygen atom to which R⁶is bonded; an aromatic hydrocarbon group which may be substituted with ahalogen atom, a hydroxyl group, a tri(C₁ -C₇)hydrocarbonsilyloxy group,a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acylgroup having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxygroup having 1 to 4 carbon atoms); an aromatic hydrocarbon group whichmay be substituted with a halogen atom, a hydroxyl group, a tri(C₁-C₇)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, analkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms; or analicyclic group which may be substituted with a halogen atom, anhydroxyl group, a tri(C₁ -C₇)hydrocarbonsilyloxy group, a carboxylgroup, an acyloxy group having 2 to 7 carbon atoms, an acyl group having2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms,an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1to 4 carbon atoms; and n represents 0, 1 or 2; can be prepared bysubjecting 2-cyclopentenones represented by the following formula(III-a): ##STR27## wherein R²¹ and R³¹ represent an aliphatichydrocarbon group having 1 to 10 carbon atoms which may have as thesubstituent --COOR⁵¹ (where R⁵¹ is an alkyl group having 1 to 10 carbonatoms); --OR⁶¹ (where R⁶¹ is an acyl group having 2 to 7 carbon atoms; atri(C₁ -C₇)hydrocarbonsilyl group; a group which forms an acetal bondtogether with an oxygen atom to which R⁶¹ is bonded; an aromatichydrocarbon group also may be substituted with a halogen atom, a tri(C₁-C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbonatoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl grouphaving 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms,and an alkoxy group having 1 to 4 carbon atoms); an aromatic hydrocarbongroup which may be substituted with a halogen atom, a tri(C₁-C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbonatoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl grouphaving 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms,and an alkoxy group having 1 to 4 carbon atoms; or an alicyclic groupwhich may be substituted with a halogen atom, a tri(C₁-C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbonatoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl grouphaving 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atomsand an alkoxy group having 1 to 4 carbon atoms; to epoxydizationreaction to obtain 2,3-epoxycyclopentanones of the following formula(IV-a-1): ##STR28## wherein R²¹ and R³¹ are as defined above, thenreacting thiols represented by the following formula (V):

    R.sup.1 --SH                                               (V)

wherein R¹ represents a substituted or non-substituted hydrocarbon grouphaving 1 to 10 carbon atoms with said 2,3-epoxycyclopentanones in thepresence of a basic compound, a alumina or silica gel, and subsequently,subjecting the reaction product, if necessary, to oxidation reaction,deprotection reaction or protection reaction.

The starting material represented by the above formula (III-a) is knownper se, and can be prepared by the method disclosed in JapaneseUnexamined Patent Publication (Kokai) No. 59-164747.

In the above formula (III-a), R²¹ and R³¹ represent an aliphatichydrocarbon group having 1 to 10 carbon atoms which may have as thesubstituent --COOR⁵¹ (where R⁵¹ is an alkyl group having 1 to 10 carbonatoms); --OR⁶¹ (where R⁶¹ represents an acyl group having 2 to 7 carbonatoms, a tri(C₁ -C₇)hydrocarbonsilyl group; a group which forms anacetal bond together with the hydrogen atom to which R⁶¹ is bonded; anaromatic hydrocarbon group which also may be substituted with a halogenatom, a tri(C₁ -C₇)hydrocarbonsilyloxy group, an acyloxy group having 2to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, analkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms); anaromatic hydrocarbon group which may be substituted with a halogen atom,a tri(C₁ -C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7carbon atoms, an acyl group having 2 to 7 carbon atoms; analkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms; or analicyclic group which may be substituted with a halogen atom, a tri(C₁-C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbonatoms, an acyl group having 2 to 7 carbon atoms an alkoxycarbonyl grouphaving 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atomsand an alkoxy group having 1 to 4 carbon atoms. As specific examples ofR²¹ and R³¹, the same specific examples as described above for R² and R³in the above formula (I), respectively, can be included.

In the process of the present invention, the compounds of the aboveformula (III-a) are subjected to epoxydization reaction. As the reagentfor the epoxydization reaction, an alkylhydroperoxide such ast-butylhydroperoxide or hydrogen peroxide may be used, but preferablyhydrogen peroxide is used. Although anhydrous hydrogen peroxide may beused, a 90 to 5% aqueous hydrogen carbon, preferably 50 to 10% aqueoushydrogen peroxide is generally used. The amount of hydrogen peroxideused may be 1 to 50 equivalents, preferably 3 to 20 equivalents,relative to 2-cyclopentenones represented by the above formula (III-a).

Preferably the epoxydization reaction is carried out in the presence ofa basic compound, and examples of such basic compounds includequaternary ammonium hydroxides such as tetramethyl ammonium hydroxide,and benzyltrimethyl ammonium hydroxide; hydroxides such as lithiumhydroxide, sodium hydroxide, and potassium hydroxide; and carbonatessuch as sodium carbonate and potassium carbonate. Preferably, alkalimetal hydroxides such as sodium hydroxide and potassium hydroxide;alkali metal carbonates such as sodium carbonates and potassiumcarbonate particularly preferably sodium hydroxide, are used. The amountof the basic compound used may be 0.01 to 5 equivalents, preferably 0.05to 2 equivalents, relative to the 2-cyclopentenones represented by theabove formula (III-a).

The reaction solvent may include alcohols such as methanol, ethanol, andt-butyl alcohol; ketones such as acetone and methyl ethyl ketone; etherssuch as dioxane, and dimethoxyethane, which are inert to hydrogenperoxide, and can be mixed with water, preferably alcohols such asmethanol, ethanol, and t-butyl alcohol, particularly preferably methanolor ethanol.

The reaction temperature of the epoxydization reaction is preferablywithin -20° to 50° C., more preferably -5° to 30° C.

The reaction time of the epoxydization reaction may differ depending onthe starting compound, the reagent, the reaction solvent is and thereaction temperature employed, but preferably is within 5 minutes to 5hours, more preferably 10 minutes to 1 hour.

After completion of the epoxydization reaction, the2,3-epoxycyclopentanones represented by the above formula (IV-a-1) canbe isolated and purified by a conventional means such as extraction,washing, drying, concentration, and chromatography, but the unpurifiedreaction mixture also can be provided as such for the subsequentreactions without isolation of said 2,3-epoxycyclopentanones.

The 2,3-epoxycyclopentanones represented by the above formula (IV-a-1)obtained in the above epoxydization reaction are novel compounds. Thereaction between the compounds of the above for (IV-a-1) and the thiolsrepresented by the above formula (V) is carried out in the presence of abasic compound, alumina or silica gel.

In the above formula (V), R¹ represents a substituted or non-substitutedhydrocarbon having 1 to 10 carbon atoms. Specific examples of R¹ includethose which are the same as the specific examples described for theabove formula (I).

When a basic compound is used in carrying out the reaction between the2,3-epoxycyclopentenones of the above formula (IV-a-1) and the thiols ofthe formula (V), such basic compounds are preferably alkali metalhydroxides or carbonates such as sodium hydroxide, potassium hydroxide,potassium carbonate, and sodium carbonate; or tertiary amines such astrimethylamine, triethylamine, and pyridine; bicyclo strong bases suchas diazabicyclo[2.2.2]octane and diazabicyclo[3.4.0]nonen; andquaternary ammonium salts such as benzyl trimethyl ammonium hydroxide.

Particularly preferably, the above tertiary amines such as triethylamineare used.

To allow a better reaction, preferably an inert solvent is used. As thesolvent to be used, any inert solvent which can dissolve the startingcompound may be used, but preferably alcohols such as methanol andethanol; ethers such as ethyl ether and tetrahydrofuran; andhydrocarbons such as hexane and benzene, are used.

The amount of the solvent used should permit the reaction to proceedsmoothly, and is preferably 1 to 100-fold volume of the startingmaterial, more preferably 2 to 20-fold volume.

The amount of the thiols (V) to be used in the present invention ispreferably stoichiometrically equimolar to the starting material(IV-a-1). The basic compound which catalyzes the reaction is preferablyused in an amount of 0.001 to 20-fold mol, more preferably 0.1 to 2-foldmol, relative to the starting material (IV-a-1).

Preferably, the reaction temperature is within -20° to 100° C., morepreferably 0° to 30° C., and preferably the reaction time for completionof the reaction is 20 minutes to 2 hours.

After the reaction, the 2-substituted-2-cyclopentenones represented bythe following formula (I-b-10): ##STR29## wherein R¹, R²¹ and R³¹ are asdefined above can be isolated and purified by treating the reactionmixture by a customary procedure. For example, isolation andpurification can be performed by extraction, washing, concentration, andchromatography, or combinations thereof, but the unpurified reactionmixture can be subjected as such to oxidation reaction, deprotectionreaction and/or protection reaction without isolation of said2-substituted-2-cyclopentenones, to produce the compounds of the aboveformula (I-b-11).

Preferably, such an oxidation reaction is carried out in an inertsolvent in the presence of an oxidizing agent.

Examples of the oxidizing agent used when producing sulfoxide preferablyinclude peracids such as hydrogen peroxide, peracetic acid, perbenzoicacid, and m-chloroperbenzoic acid; and sodium metaperiodate, seleniumdioxide, chromic acid, iodosylbenzene, hypochlorous acid, and t-butylhydroperoxide; and when producing sulfone, preferably include hydrogenperoxide, hydrogen peroxide and a tungsten oxide or vanadium oxidecatalyst, peracetic acid, perbenzoic acid, m-chloroperbenzoic acid,ruthenium oxide, and osmium tetraoxide.

As the inert organic solvent, for example, preferably acetic acid,methylene chloride, chloroform, 1,2-dicycloroethane, benzene, and ethylacetate are used.

Preferably the reaction temperature is within -78° C. to 50° C., morepreferably -20° C. to 30° C.

The reaction time may differ depending on the starting compound, thereaction temperature, and the kind of oxidizing agent, but preferably is30 minutes to 38 hours.

For example, when a sulfoxide is to be produced by using an oxidizingagent which can produce both sulfoxide and sulfone, preferably theamount of the oxidizing agent is not enough to produce sulfone, forexample, an amount of about 1 to about 1.5 equivalents relative to the(I-b-10) used, and the reaction is monitored by thin layerchromatography (i.e., TLC).

After completion of the reaction, the desired compound can be isolatedand purified by conventional methods such as extraction, washing,concentration, and chromatography.

Further, a desired compound having protective groups in the molecularcan be subjected to deprotection reaction.

Elimination of the protective group, when the protective group is agroup forming an acetal bond together with oxygen atom of hydroxylgroup, is preferably carried out by using acetic acid, and a pyridiniumsalt of p-toluenesulfonic acid or cation ion exchange resin as thecatalyst, and by using a reaction solvent such as water,tetrahydrofuran, ethyl ether, dioxane, acetone, and acetonitrile.Preferably the reaction is carried out at a temperature of from -78° C.to +30° C., for about 10 minutes to 3 days. When the protective group isa tri(C₁ -C₇)hydrocarbonsilyl group, the reaction may be practiced inthe reaction solvent as mentioned above in the presence of, for example,acetic acid, hydrogen fluoride-pyridine, tetrabutylammonium fluoride,and cesium fluoride at the same temperature and for the same time. Whenthe protective group is an acyl group, the reaction may be practiced bycarrying out hydrolysis in, for example, an aqueous solution of sodiumhydroxide, potassium hydroxyde, and calcium hydroxide, or awater-alcohol mixture or a methanol or ethanol solution containingsodium methoxide, potassium methoxide, and sodium ethoxide.

An ester group in the required compound can be subjected to hydrolysis,which can be carried out by using an enzyme such as lipase in water or asolvent containing water at a temperature of from -10° C. to +60° C.,for about 10 minutes to 24 hours.

When the desired compound has a carboxyl group in the molecule, thecompound can be further subjected to a salt forming reaction, to obtaina corresponding carboxylic acid salt. The salt forming reaction is knownper se, and may be practiced by carrying out the neutralization reactionwith a basic compound such as sodium hydroxide, potassium hydroxyde,sodium carbonate, or ammonia, trimethylamine, monoethanolamine, andmorpholine, by a customary procedure, in an amount substantially equalto the carboxylic acid.

Further, a desired compound having a hydroxyl group in the molecule canbe subjected to protection reaction.

Known methods can be employed for the protection reaction of thehydroxyl group. For example, when the protective group is an acyl groupsuch as an acetyl group, propionyl group, or benzoyl group, theprotective group can be easily introduced by reacting an acid halide oran acid anhydride with pyridine. When the protective group is atrihydrocarbonsilyl group such as a trimethylsilyl group ort-butyldimethylsilyl group, the protective group can be introduced byreacting a trihydrocarbonsilyl halide in the pressure of amines such astriethylamine and dimethylaminopyridine. When the protective group is atetrahydropyran-2-yl group tetrahydrofuran-2-yl group, or 1-ethoxyethylgroup, the protective group can be introduced by placing the compound incontact with dihydropyrane, dihydrofuran, or ethyl vinyl ether, which isa corresponding vinyl other compound, in the presence of an acidiccatalyst such as p-toluenesulfonic acid, and thus novel2-substituted-2-cyclopentenones represented by the above formula(I-b-11) are prepared.

When alumina or silica gel is used during the reaction between the2,3-epoxycyclopentenones of the above formula (IV-a-1) and the thiols ofthe formula (V), such alumina or silica gel may be silica gel or aluminaused generally during a separation and purification of an organiccompound. For the silica gel, for example, Wakol Gel C-300, Wakol GelC-200 may be employed. Similarly, for the alumina, for example,preferably basic alumina (basic alumina produced by Woelm Co.), acidicalumina (neutral alumina produced by Woelm Co.), and active alumina areused, more preferably, basic alumina.

To allow a better reaction, preferably an inert solvent is used. As thesolvent, any inert solvent which can dissolve the starting compound maybe used, but preferably alcohols such as methanol and ethanol, etherssuch as ethyl ether and tetrahydrofuran, and hydrocarbons such as hexaneand benzene are employed.

The amount of the solvent should permit the reaction to proceedsmoothly, but preferably 1 to 100-fold volumes of the starting material,more preferably 2 to 20-fold volumes are employed.

The amount of the thiols (V) to be used in the present invention ispreferably stoichiometrically equimolar to the starting material(IV-a-1). The silica gel and alumina which catalyse the reaction ispreferably used in an amount of 0.1 to 20-fold weight, more preferably0.5 to 5-fold weight, relative to the starting material (IV-a-1).

Preferably, the reaction temperature is within -20° to 100° C., morepreferably 0° to 30° C. The reaction time may differ depending on thecatalyst amount and the solvent used, but preferably the reaction iscompleted within 10 minutes to 24 hours.

After the reaction, the 2-substituted-2-cyclopentenones represented bythe above formula (I-b-10) can be obtained only by filtering thereaction mixture to remove alumina and silica gel, and evaporating thereaction solvent, but for a further purification, they also can beobtained by the methods of, for example, recrystallization andchromatography, or a combination thereof.

Of the 2-substituted-2-cyclopentenones of the above formula (I) of thepresent invention, the 2-substituted-2-cyclopentenones according toclaim 1 represented by the following formula (I-a-1). ##STR30## whereinR¹, R², R³⁴ and n are as defined above; the representation denotes thatthe substituent bonded to the double bond is in an E-configuration or aZ-configuration or mixtures thereof at any desired ratio; can beproduced according to the present invention by dehydrating the2-substituted-2-cyclopentenones represented by the following formula(I-b-10): ##STR31## wherein R¹, R²¹ and R³¹ are as defined above, andsubjecting the dehydrated product to oxidation, deprotection reactionand/or protection reaction.

In the above formula (I-b-10), R¹ represents a substituted ornon-substituted hydrocarbon group having 1 to 10 carbon atoms. Specificexamples of R¹ include the same specific examples as described above forthe formula (I).

In the above formula (I-b-10), R²¹ and R³¹ represent an aliphatichydrocarbon group having 1 to 10 carbon atoms which may have as thesubstituent -COOR⁵¹ (where R⁵¹ is an alkyl group having 1 to 10 carbonatoms) or --OR⁶¹ (where R⁶¹ is an acyl group having 2 to 7 carbon atoms;a tri(C₁ -C₇)hydrocarbonsilyl group, a group which forms an acetal bondtogether with the oxygen atom to which R⁶¹ is bonded; an aromatichydrocarbon group which may be substituted with a halogen atom, a tri(C₁-C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbonatoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl grouphaving 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms,and an alkoxy group having 1 to 4 carbon atoms); an aromatic hydrocarbongroup which may be substituted with a halogen atom, a tri(C₁-C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbonatoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl grouphaving 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms,and an alkoxy group having 1 to 4 carbon atoms; or an alicyclic groupwhich may be substituted with a halogen atom, a tri(C₁-C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbonatoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl grouphaving 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atomsand an alkoxy group having 1 to 4 carbon atoms. In the above formula(I-b-10), specific examples of R²¹ and R³¹ include the same specificexamples as described for R² and R³ in the above formula (I).

In the process of the present invention, the compounds of the aboveformula (I-b-10) are subjected to dehydration reaction. Dehydrationreaction is preferably carried out by using a basic compound and areactive derivative of an organic sulfuric acid. More specifically, thecompound of the above formula (I-b-10) is preferably first treated witha basic compound and a reactive derivative of an organic sulfonic acid,and further treated with a basic compound. The dehydration reaction iscompleted by a sulfonylation of the hydroxyl group of the compound ofthe formula (I-b-11), and then elimination of an organic sulfonic acid.

Preferably, amines are used as the basic compound together with thederivative of an organic sulfonic acid, and examples of such aminesinclude pyridine, 4-dimethylaminopyridine, triethylamine,diisopropylcyclohexylamine, 1,5-diazabicyclo[4.3.0]non-5-ene(hereinafter abbreviated as DBN), 1,8-diazabicyclo[5.4.0]undec-7-ene(hereinafter abbreviated as DBU), quinacridine, triethylenediamine,isopropyldimethylamine, and diisopropylethylamine. Particularly,preferably are pyridine, 4-dimethylaminopyridine, DBU, and DBN.

Examples of reactive derivatives of organic sulfonic acid includeorganic sulfonic acid halides such as methanesulfonylchloride,ethanesulfonylchloride, n-butanesulfonylchloride,t-butanesulfonylchloride, trifluoromethanesulfonylchloride,benzenesulfonylchloride, and p-toluenesulfonylchloride; and anhydrousorganic sulfonic acids such as anhydrous methanesulfonic acid, anhydrousethanesulfonic acid, anhydrous trifluoromethanesulfonic acid, anhydrousbenzenesulfonic acid, and anhydrous p-toluenesulfonic acid.

The basic compound itself as mentioned above may be also used as thesolvent, but preferably halogenated hydrocarbons such asdichloromethane, chloroform, carbon tetrachloride, and dichloroethane;ethers such as ether and tetrahydrofuran; and hydrocarbons such asbenzene, toluene, pentane, hexane, and cyclohexane are used. Mostpreferably, pyridine and dichloromethane is used.

Preferably, the derivative of an organic sulfonic acid is used at aratio of 1 to 10 equivalents relative to 1 mol of the compound of theabove formula (I-b-10).

Preferably, the basic compound is used at a ratio of 1 equivalent ormore, most preferably 2 or more equivalents, relative to the reactivederivatives of the organic sulfonic acid employed.

Preferably, the amount of the solvent used is 1 to 1000-fold volume,more preferably 5 to 100-fold volume, relative to the compoundrepresented by the above formula (I-b-10). The reaction temperature maydiffer depending on the starting compound, the basic compound, and thesolvent, etc. employed, but preferably is from -40° C. to 100° C., morepreferably from 0° C to 30° C. The reaction time depends on theconditions, but preferably is about 0.1 to 10 hours. The progress of thereaction is monitored by a method such as thin layer chromatography.

Therefore, according to the above reaction (hereinafter referred to asthe first reaction), an organic sulfonyloxyoxy derivative is formed inwhich the hydroxyl group on the alkyl group at the 5-position of the2-substituted-2-cyclopentenones of the above formula (I-b-10) isconverted to an organic sulfonyloxy group, and the compound issubsequently treated with a basic compound (hereinafter referred to asthe second reaction) to eliminate a corresponding organic sulfonic acid,thereby giving 2-substituted-2-cyclopentenones represented by thefollowing formula (I-a-10): ##STR32## wherein R¹, R²¹ R³¹ and therepresentation are as defined above.

As the basic compound which can be used in the second reaction, the samebasic compounds as mentioned in the above first reaction may beincluded, or the basic compound used in the second reaction may bedifferent from that used in the first reaction.

The second reaction can be permitted to proceed within the sametemperature range. Also, the organic sulfonyloxy derivative may beisolated and then subjected to the second reaction, or the firstreaction and the second reaction may be carried out in the same reactionsystem. After completion of the reaction, the desired compound can beisolated and purified by conventional means such as extraction, washing,concentration, chromatography or combinations thereof, but if necessary,the unpurified reaction mixture can be subjected as such to oxidation,deprotection reaction and/or protection reaction without isolation ofsaid 2-substituted-2-cyclopentenones, whereby2-substituted-2-cyclopentenones of the above formula (I-a-1) can beprepared. Such oxidation reaction, deprotection reaction or protectionreaction can be accomplished by the same methods as used for producingthe 2-substituted-2-cyclopentenones represented by the above formula(I-b-11) from the 2-substituted-2-cyclopentenones represented by theabove formula (I-b-10).

Of the 2-substituted-2-cyclopentenones of the above formula (I) of thepresent invention, the 2-substituted-2-cyclopentenones represented bythe above formula (I-a-1) and the 2-substituted-2-cyclopentenonesrepresented by the following formula (I-b-12): ##STR33## wherein R¹, R²,R³⁴ and n are as defined above and m is 0,1 or 2 can be producedaccording to the present invention by allowing 2,3-epoxycyclopentanonesrepresented by the following formula (IV-a-2): ##STR34## wherein R²¹,R³¹ and the representation are as defined above to react with thiolsrepresented by the following formula (V):

    R.sup.1 --SH                                               (V)

wherein R¹ is the same as defined above in the presence of a basiccompound, alumina or silica gel, and then carrying out an oxidationreaction, deprotection reaction and/or protection reaction, if desired.

The starting material represented by the above formula (IV-a-2) is amaterial known per se, and can be prepared by, for example, the methoddescribed in Japanese Unexamined Patent Publication (Kokai) No.61-47437.

In the above formula (IV-a-2), R²¹ and R³¹ represent an aliphatichydrocarbon group having 1 to 10 carbon atoms which may have as thesubstituent --COOR⁵¹ (where R⁵¹ is an alkyl group having 1 to 10 carbonatoms); --OR⁶¹ (where R⁶¹ is an acyl group having 2 to 7 carbon atoms; atri(C₁ -C₇)hydrocarbonsilyl group; a group which forms an acetal bondtogether with the oxygen atom to which R⁶¹ is bonded; an aromatichydrocarbon group which may be substituted with a halogen atom, a tri(C₁-C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbonatoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl grouphaving 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms,and an alkoxy group having 1 to 4 carbon atoms); an aromatic hydrocarbongroup which may be substituted with a halogen atom, a tri(C₁-C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbonatoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl grouphaving 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms,and an alkoxy group having 1 to 4 carbon atoms; or an alicyclic groupwhich may be substituted with a halogen atom, a tri(C₁-C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbonatoms, a acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl grouphaving 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atomsand an alkoxy group having 1 to 4 carbon atoms. In the above formula(IV-a-2), specific examples of R²¹ and R³¹ include the same specificexamples as mentioned above for R² and R³ in the above formula (I).

In the above formula (V), R¹ represents a substituted or non-substitutedhydrocarbon group having 1 to 10 carbon atoms, specific examples of R¹may include the same specific examples as mentioned above for the aboveformula (I).

In the process of the present invention, the reaction is carried outbetween the 2,3-epoxycyclopentanones represented by the above formula(IV-a-2) and the thiols represented by the above formula (V) in thepresence of a basic compound, alumina or silica gel, and then thereaction product is subjected to oxidation reaction, deprotectionreaction and/or protection reaction, if desired, whereby the2-substituted-2-cyclopentenones represented by the above formula (I-a-1)and (I-b-12) can be obtained. Such production processes can beaccomplished by the same processes for producing2-substituted-2-cyclopentenones represented by the above formula(I-b-11) from the 2,3-epoxycyclopentenones represented by the aboveformula (IV-a-1) and the thiols represented by the above formula (V).

Of the 2-substituted-2-cyclopentenones of the above formula (I) of thepresent invention, the 2-substituted-2-cyclopentenones represented bythe following formula (I-b-2): ##STR35## wherein R¹, R², R³⁴ and n areas defined above; and R⁴ represents a hydrogen atom or a protected groupof the protected hydroxyl group; can be prepared according to thepresent invention by subjecting the 2-substituted-2-cyclopentenonesrepresented by the following formula (III-b): ##STR36## wherein R³¹represents an aliphatic hydrocarbon group having 1 to 10 carbon atomswhich may be as the substituent --COOR⁵¹ (where R⁵¹ is an alkyl grouphaving 1 to 10 carbon atoms); --OR⁶¹ (where R⁶¹ is an acyl group having2 to 7 carbon atoms; a tri(C₁ -C₇)hydrocarbonsilyl group; a group whichforms an acetal bond together with the oxygen atom to which R⁶¹ isbonded; an aromatic hydrocarbon group which may be substituted with ahalogen atom, a tri(C₁ -C₇)hydrocarbonsilyloxy group, an acyloxy grouphaving 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, analkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms); anaromatic hydrocarbon group which may be substituted with a halogen atom,a tri(C₁ -C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7carbon atoms, an acyl group having 2 to 7 carbon atoms, analkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms; or analicyclic group which may be substituted with a halogen atom, a tri(C₁-C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbonatoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl grouphaving 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atomsand an alkoxy group having 1 to 4 carbon atoms; and R⁴⁰ represents ahydrogen atom or a protected group of the protected hydroxyl group toepoxydization reaction to obtain the 2,3-epoxycyclopentanonesrepresented by the following formula (IV-b-1): ##STR37## wherein R³¹ andR⁴⁰ are the same as defined above, which can be subjected todeprotection of R³¹, if desired, to result in R³⁴, then reacting the2,3-epoxycyclopentanones with the thiols represented by the followingformula (V):

    R.sup.1 --SH                                               (V)

wherein R¹ is as defined above, further protecting the hydroxyl group,if desired, to obtain the 2-substituted-2-cyclopentenones represented bythe following formula (I-c-1): ##STR38## wherein R¹, R³⁴, and R⁴⁰ arethe same as defined above; and for the further reaction, coverting R³⁴to R³¹ and R⁴⁰ to R⁴¹ which represents a protective group of theprotected hydroxyl group, subjecting this to aldol condensation reactionwith aldehydes represented by the following formula (II):

    OHC--R.sup.21                                              (II)

wherein R²¹ is as defined above, and subsequently subjecting thereaction product to oxidation reaction, deprotection reaction and/orprotection reaction, if desired.

The starting material represented by the above formula (III-b) is amaterial known per se, and may be prepared by the method described inJapanese Unexamined Patent Publication (Kokai) No. 62-96438. In theabove formula (III-b), R³¹ represents an aliphatic hydrocarbon grouphaving 1 to 10 carbon atoms which may have as the substituent --COOR⁵¹(where R⁵¹ is an alkyl group having 1 to 10 carbon atoms); --OR⁶¹ (whereR⁶¹ is an acyl group having 2 to 7 carbon atoms; a tri(C₁-C₇)hydrocarbonsilyl group; a group which forms an acetal bond togetherwith the oxygen atom to which R⁶¹ is bonded; an aromatic hydrocarbongroup which may be substituted with a halogen atom, an acyloxy grouphaving 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, analkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms); anaromatic hydrocarbon group which may be substituted with a halogen atom,a tri(C₁ -C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7carbon atoms, an acyl group having 2 to 7 carbon atoms, analkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms; or analicyclic group which may be substituted with a halogen atom, a tri(C₁-C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbonatoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl grouphaving 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atomsand an alkoxy group having 1 to 4 carbon atoms. Specific examples of R³¹include the same specific examples as mentioned above for R³ in theabove formula (I). In the above formula (III-b), R⁴⁰ represents ahydrogen atom or a protected group of the protected hydroxyl group.Specific examples of R⁴⁰ include a hydrogen atom; alkyl groups such asmethyl, ethyl, propyl, and isopropyl; tri(C₁ -C₇)hydrocarbonsilyloxygroups such as trimethylsilyl, triethylsilyl, t-butyldimethylsilyl,t-butyldiphenylsilyl, and tribenzylsilyl; groups which form an acetalbond together with the oxygen atom to which R⁴⁰ is bonded such asmethoxymethyl, 1-ethoxyethyl, 2-methoxyethoxymethyl, andtetrahydropyran-2-yl; and acyl groups such as acetyl, propionyl, andbutyryl.

In the process of the present invention, the compound of the aboveformula (III-b) is subjected to epoxydization reaction to obtain the2,3-epoxycyclopentanones of the above formula (IV-b-1). Theepoxydization reaction method can be the same method used forpreparation of the 2,3-epoxycyclopentanones represented by the aboveformula (IV-a-1) by subjecting the 2-cyclopentenones represented by theabove formula (III-a) to epoxydization reaction.

The 2,3-epoxycyclopentanones represented by the above formula(IV-b-1)obtained in the above epoxydization reaction are novelcompounds. The reaction between the compounds of the above formula(IV-b-1) and the thiols represented by the above formula (V) is carriedout in the presence of a basic compound, alumina or silica gel.

In the above formula (V), R¹ represents a substituted or non-substitutedhydrocarbon group having 1 to 10 carbon atoms. Specific examples of R¹include the same specific examples as mentioned above for the aboveformula (I).

In the process of the present invention, the reaction is carried outbetween the 2,3-epoxycyclopentanones represented by the above formula(IV-b-1) and the thiols represented by the above formula (V) in thepresence of a basic compound, alumina or silica gel, and then thereaction product is subjected to protection reaction to obtain the2-substituted-2-cyclopentenones represented by the above formula(I-c-1), if desired. This production process can be accomplished by thesame process used for producing the 2-substituted-2-cyclopentenonesrepresented by the above formula (I-b-10) from the2,3-epoxycyclopentanones represented by the above formula (IV-a-1) andthe thiols represented by the above formula (V).

The 2-substituted-2-cyclopentenones represented by the above formula(I-c-1) obtained in the above reaction are novel compounds. In the aboveformula (I-c-1), R⁴¹ represents a protected group of the protectedhydroxyl group. Specific examples of R⁴¹ include alkyl groups such asmethyl, ethyl, propyl, and isopropyl; tri(C₁ -C₇)hydrocarbonsilyloxygroups such as trimethylsilyl, triethylsilyl, t-butyldimethylsilyl,t-butyldiphenylsilyl, and tribenzylsilyl; groups which form an acetalbond together with the oxygen atom to which R⁴¹ is bonded such asmethoxymethyl, 1-ethoxyethyl, 2-methoxyethoxymethyl, andtetrahydropyran-2-yl; and acyl groups such as acetyl, propionyl, andbutyryl.

In the process of the present invention, the compounds represented bythe above formula (I-c-1) and the aldehydes represented by the aboveformula (II) are subjected to aldol condensation reaction.

In the above formula (II), R²¹ represents an aliphatic hydrocarbon grouphaving 1 to 10 carbon atoms which may have as the substituent --COOR⁵¹(where R⁵¹ is an alkyl group having 1 to 10 carbon atoms); --OR⁶¹ (whereR⁶¹ is an acyl group having 2 to 7 carbon atoms; a tri(C₁-C₇)hydrocarbonsilyl group; a group which forms an acetal bond togetherwith the oxygen atom to which R⁶¹ is bonded; an aromatic hydrocarbongroup which may be substituted with a halogen atom, a tri(C₁-C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbonatoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl grouphaving 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms,and an alkoxy group having 1 to 4 carbon atoms); an aromatic hydrocarbongroup which may be substituted with a halogen atom, a tri(C₁-C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbonatoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl grouphaving 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms,and an alkoxy group having 1 to 4 carbon atoms; or an alicyclic groupwhich may be substituted with a halogen atom, a tri(C₁-C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbonatoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl grouphaving 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atomsand an alkoxy group having 1 to 4 carbon atoms. Specific examples of R²¹include the same specific examples as mentioned above for R² in theabove formula (I).

In the process of the present invention, the compounds represented bythe above formula (I-c-1) and the aldehydes represented by the aboveformula (II) are subjected to aldol condensation reaction.

The aldol condensation reaction is carried out in the presence of abasic compound in a solvent. Examples of the basic compound and thereaction solvent include those described in: A. T. Nielsen, W. J.Haulihan, Organic Reaction (Org. React.), 16, 1 (1968); H. O. House,"Modern Synthetic Reactions" 2nd Ed., Benjamin (1972), p. 629; and NewExperimental Chemistry Course 14, II736, III851, etc.

For the aldol condensation reaction, preferably metal amides such aslithium diisopropylamide, lithium diethylamide, and lithiumbistrimethylsilylamide; or dialkylborontrifluoromethanesulfonic acidssuch as dibutylborontrifluoromethanesulfonic acid in the presence of atertiary amine such as triethylamine, diisopropylethylamine, andtributylamine, are employed.

When the aldol condensation reaction is carried out by using a metalamide, preferably the amount thereof is 0.2 to 50 equivalents, morepreferably 0.9 to 10 equivalents, relative to the compound of the aboveformula (I-c-1). As the reaction solvent, for example, ethers such asether and tetrahydrofuran; and hydrocarbons such as petroleum ether,hexane, and pentane, may be employed. Preferably the reactiontemperature is from -150° C. to 100° C., more preferably from -80° C. to0° C.

When the aldol condensation reaction is carried out by using a tertiaryamine and a dialkylboryl trifluoromethanesulfonate, preferably theamounts used thereof are, for example, 0.5 to 50 equivalents, morepreferably 1 to 10 equivalents, relative to the compound of the aboveformula (I-c-1).

The aldehyde of the formula (II), which is the other starting material,preferably is used at a ratio of 0.5 to 10 equivalents, more preferably0.8 to 2 equivalents, relative to the compound of the formula (I-c-1).

The reaction time depends on the starting compound, the reagents, andthe reaction solvent employed, but preferably is from 5 minutes to 48hours, more preferably from 10 minutes to 12 hours.

After completion of the reaction, the 2-substituted-2-cyclopentenonesrepresented by the following formula (I-b-20): ##STR39## wherein R¹,R²¹, R³¹ and R⁴¹ are as defined above can be obtained by isolating andpurifying the reaction mixture by a conventional means such asextraction, water washing, drying, and chromatography, but theunpurified reaction mixture can be subjected to an oxidation reaction,deprotection reaction or protection reaction without isolation of said2-substituted-2-cyclopentenones, whereby the compound of the aboveformula (I-b-2) can be prepared. Such an oxidation reaction,deprotection reaction or protection reaction can be carried out by thesame methods as used in the preparation of the2-substituted-2-cyclopentenones represented by the above formula(I-b-11) from the 2-substituted-2-cyclopentenones represented by theabove formula (I-b-10).

Of the 2-substituted-2-cyclopentenones of the above formula (I) of thepresent invention, the 2-substituted-2-cyclopentenones represented bythe following formula (I-a-2): ##STR40## wherein R¹, R² R³⁴, R⁴, n andthe representation are as defined above can be prepared by dehydratingthe 2-substituted-2-cyclopentenones represented by the following formula(I-b-20): ##STR41## wherein R¹, R²¹ R³¹ and R⁴¹ are as defined above,and subsequently subjecting the dehydrated product to an oxidationreaction, deprotection reaction and/or protection reaction, if desired.

In the above formula (I-b-20), R¹ represents a substituted ornon-substituted hydrocarbon group having 1 to 10 carbon atoms, andspecific examples of R¹ include the same specific examples as mentionedabove for the above formula (I).

In the above formula (I-b-20), R²¹ and R³¹ represent an aliphatichydrocarbon group having 1 to 10 carbon atoms which may have as thesubstituent --COOR⁵¹ (where R⁵¹ is an alkyl group having 1 to 10 carbonatoms) or --OR⁶¹ (where R⁶¹ is an acyl group having 2 to 7 carbon atoms;a tri(C₁ -C₇)hydrocarbonsilyl group; a group which forms an acetal bondtogether with the oxygen atom to which R⁶¹ is bonded; an aromatichydrocarbon group which may be substituted with a halogen atom, a tri(C₁-C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbonatoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl grouphaving 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms,and an alkoxy group having 1 to 4 carbon atoms); an aromatic hydrocarbongroup which may be substituted with a halogen atom, a tri(C₁-C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbonatoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl grouphaving 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms,and an alkoxy group having 1 to 4 carbon atoms; or an alicyclic groupwhich may be substituted with a halogen atom, a tri(C₁-C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbonatoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl grouphaving 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms,or an alkoxy group having 1 to 4 carbon atoms. Specific examples of R²¹and R³¹ in the above formula (I-b-20) include the same specific examplesas mentioned above for R² and R³, respectively for the above formula(I).

In the above formula (I-b-20), R⁴¹ represents a protected group of theprotected hydroxyl group. Specific examples of R⁴¹ include alkyl groupssuch as methyl, ethyl, propyl, and isopropyl; tri(C₁-C₇)hydrocarbonsilyl groups such as trimethylsilyl, triethylsilyl,t-butyldimethylsilyl, t-butyldiphenylsilyl, and tribenzylsilyl; groupswhich form an acetal bond together with the oxygen atom to which R⁴¹ isbonded such as methoxymethyl, 1-ethoxyethyl, 2-methoxyethoxymethyl, andtetrahydropyran-2-yl; and acyl groups such as acetyl, propionyl, andbutyryl.

In the process of the present invention, the compound of the aboveformula (I-b-20) is subjected to dehydration reaction. This dehydrationreaction can be carried out by the same method as used in thepreparation of the 2-substituted-2-cyclopentenones represented by theabove formula (I-b-10) from the 2-substituted-2-cyclopentenonesrepresented by the above formula (I-b-10), whereby2-substituted-2-cyclopentenones represented by the following formula(I-a-20): ##STR42## wherein R¹, R²¹, R³¹, R⁴¹ and the representation areas defined above can be obtained.

The compound of the above formula (I-a-20) can be further subjected tooxidation reaction, deprotection reaction or protection reaction, ifdesired, to be converted to 2-substituted-2-cyclopentenones of the aboveformula (I-a-2). This oxidation reaction, deprotection reaction and/orprotection reaction can be carried out by the same method as used in thepreparation of the 2-substituted-2-cyclopentenones represented by theabove formula (I-b-11) from the 2-substituted-2-cyclopentenonesrepresented by the above formula (I-b-10).

Of the 2-substituted-2-cyclopentenones of the above formula (I) of thepresent invention, the 2-substituted-2-cyclopentenones represented bythe following formula (I-a-3'), which are most preferably among theabove formula (I-a-3): ##STR43## wherein R¹, R², n and therepresentation are as defined above; and R³³ represents a hydrogen atomor an aliphatic hydrocarbon group having 1 to 9 carbon atoms having asthe substituent --COOR⁵ (where R⁵ represents hydrogen atom, an alkylgroup having 1 to 10 carbon atoms or one equivalent cation); --OR⁶(where R⁶ is an acyl group having 2 to 7 carbon atoms; a tri(C₁-C₇)hydrocarbonsilyl group; a group which forms an acetal bond togetherwith the oxygen atom to which R⁶ is bonded; an aromatic hydrocarbongroup which may be substituted with a halogen atom, a hydroxyl group, atri(C₁ -C₇)hydrocarbonsilyloxy group, a caroboxyl group, an acyloxygroup having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbonatoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkylgroup having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4carbon atoms); an aromatic hydrocarbon group which may be substitutedwith a halogen atom, a hydroxyl group, a tri(C₁ -C₇)hydrocarbonsilyloxygroup, a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, anacyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and analkoxy group having 1 to 4 carbon atoms; or an alicyclic group which maybe substituted with a halogen atom, a hydroxyl group, a tri(C₁-C₇)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, analkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms; can beprepared according to the present invention by subjecting the2-substituted-2-cyclopentenones represented by the formula (I-a-21):##STR44## wherein R¹, R²¹, R⁴, n and the representation are as definedabove; and R³² represents a hydrogen atom or an aliphatic hydrocarbongroup having 1 to 9 carbon atoms which may have as the substituent--COOR⁵¹ (where R⁵¹ is an alkyl group having 1 to 10 carbon atoms);--OR⁶¹ (where R⁶¹ is an acyl group having 2 to 7 carbon atoms; a tri(C₁-C₇)hydrocarbonsilyl group; a group which forms an acetal bond togetherwith the oxygen atom to which R⁶¹ is bonded; an aromatic hydrocarbongroup which may be substituted with a halogen atom, a tri(C₁-C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbonatoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl grouphaving 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms,and an alkoxy group having 1 to 4 carbon atoms); an aromatic hydrocarbongroup which may be substituted with a halogen atom, a tri(C₁-C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbonatoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl grouphaving 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms,and an alkoxy group having 1 to 4 carbon atoms; or an alicyclic groupwhich may be substituted with a halogen atom, a tri(C₁-C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbonatoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl grouphaving 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atomsand an alkoxy group having 1 to 4 carbon atoms; and subsequentlysubjecting the reaction product to an oxidation reaction, deprotectionreaction and/or protection reaction, if desired.

In the above formula (I-a-21), R¹ is substituted or non-substitutedhydrocarbon group having 1 to 10 carbon atoms, and specific examples ofR¹ include the same specific examples as mentioned above for the aboveformula (I).

In the above formula (I-a-21), R²¹ is an aliphatic hydrocarbon grouphaving 1 to 10 carbon atoms which may have as the substituent --COOR⁵¹(where R⁵¹ is an alkyl group having 1 to 10 carbon atoms); --OR⁶¹ (whereR⁶¹ is an acyl group having 2 to 7 carbon atoms; a tri(C₁-C₇)hydrocarbonsilyl group; a group which forms an acetal bond togetherwith the oxygen atom to which R⁶¹ is bonded; an aromatic hydrocarbongroup which may be substituted with a halogen atom, a tri(C₁-C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbonatoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl grouphaving 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms,and an alkoxy group having 1 to 4 carbon atoms); an aromatic hydrocarbongroup which may be substituted with a halogen atom, a hydroxyl group, acarboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acylgroup having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxygroup having 1 to 4 carbon atoms; or an aliphatic group which may besubstituted with a halogen atom, a tri(C₁ -C₇)hydrocarbonsilyloxy group,an acyloxy group having 2 to 7 carbon atoms, an acyloxy group having 2to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms,an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1to 4 carbon atoms. Specific examples of R²¹ include the same specificexamples as mentioned for R¹ in the above formula (I).

In the above formula (I-a-21), R³² represents a hydrogen atom or analiphatic hydrocarbon group having 1 to 9 carbon atoms which may have asthe substituent --COOR⁵¹ (where R⁵¹ is an alkyl group having 1 to 10carbon atoms); --OR⁶¹ (where R⁶¹ is an acyl group having 2 to 7 carbonatoms; a tri(C₁ -C₇)hydrocarbonsilyl group; a group which forms anacetal bond together with the oxygen atom to which R⁶¹ is bonded; anaromatic hydrocarbon group which may be substituted with a halogen atom,a tri(C₁ -C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7carbon atoms, an acyl group having 2 to 7 carbon atoms, analkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms); anaromatic hydrocarbon group which may be substituted with a halogen atom,a tri(C₁ -C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7carbon atoms, an acyl groups having 2 to 7 carbon atoms, analkoxycarbonyl group having 2 to 5 carbon atoms, an alkoxy group having1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms; oran alicyclic group which may be substituted with a halogen atom, atri(C₁ -C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7carbon atoms, an acyl group having 2 to 7 carbon atoms, analkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms.Specific examples of R³² include the same specific examples as mentionedfor R³³ in the above formula (I").

In the above formula (I-a-21), R⁴ represents a hydrogen atom, or aprotected group of protected hydroxyl group. Specific examples of R⁴include a hydrogen atom; alkyl groups such as methyl, ethyl, propyl, andisopropyl; tri(C₁ -C₇)hydrocarbonsilyl groups such as trimethylsilyl,triethylsilyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, andtribenzylsilyl; groups which form an acetal bond together with theprotective group of the protected hydroxyl group such as methoxymethyl,1-ethoxyethyl, 2-methoxyethoxymethyl, and tetrahydropyran-2-yl and acylgroups such as acetyl, propionyl, and butylyl.

According to the present invention, the 2-substituted-2-cyclopentenonesrepresented by the above formula (I-a-21) can be prepared by forming analkylidene group at the 4-position of the cyclopentenone skeleton by anelimination reaction, carrying out the oxidation reaction when S bondedat the 2-position is to be converted to sulfoxide or sulfone, andfurther, subjecting the reaction product to a deprotection reaction of ahydroxyl group or carboxyl group, and/or a protection reaction.

In the process of the present invention, the compound of the aboveformula (I-a-21) is subjected to an elimination reaction, which ispreferably practiced by using an acidic compound. As the acidiccompound, there may be employed organic carboxylic acids such as aceticacid, propanoic acid, butanoic acid, oxalic acid, malonic acid, tartaricacid, and benzoic acid; inorganic acids such as hydrochloric acid,sulfuric acid, nitric acid, and hydrofluoric acid; organic sulfonicacids such as p-toluenesulfonic acid, methanesulfonic acid, andbenzenesulfonic acid, but preferably, acetic acid is used.

The solvent to be used includes water; alcohols such as methanol andethanol; ethers such as ether, tetrahydrofuran, dioxane, anddimethoxyethane; aprotic polar solvents such as hexamethylphosphorictriamide, dimethylformamide, and dimethylsulfoxide; halogenatedhydrocarbons such as dichloromethane and chloroform; and acetonitrileand nitromethane, which may be used alone or as a mixture thereof.

The acidic compound may be be used at a ratio preferably of 0.001 to1000 equivalents per 1 mol of the compound of the above formula(I-a-21).

Preferably, the amount of the solvent used is 1 to 1000-fold volume,more preferably 5 to 100-fold volume, relative to the compoundrepresented by the above formula (I-a-21). The reaction temperature maydiffer depending on the starting compound, the acidic compound, and theamount of solvent employed, but preferably is from -20° C. to 100° C.,more preferably from 0° C. to 50° C. The reaction time, which is differsdepending on the conditions, is about 0.1 to 100 hours. The progress ofthe reaction is monitored by a method such as chromatography.

After completion of the reaction, the desired compound may be purifiedby a conventional means such as extraction, washing, concentration, andchromatography, or combination thereof, but the unpurified reactionmixture can be subjected as such, without isolation of the desiredcompound, to an oxidation reaction, deprotection reaction or protectionreaction, if desired, to prepare the 2-substituted-2-cyclopentenonesrepresented by the above formula (I-a-3). This oxidation reaction,deprotection reaction and/or protection reaction can be carried out bythe same method as used in the preparation of the2-substituted-2-cyclopentenones represented by the above formula(I-b-11) from the 2-substituted-2-cyclopentenones represented by theabove formula (I-b-10).

Of the 2-substituted-2-cyclopentenones of the above formula (I) of thepresent invention, the 2-substituted-2-cyclopentenones represented bythe following formula (I-2): ##STR45## wherein R¹, R², R³ and X are asdefined above; A¹¹ and B are such that A¹¹ represents a hydroxyl groupor ##STR46## and B represents a hydrogen atom or A¹¹ and B togetherrepresent a single bond; k is 1 or 2; and i is 0, 1, or 2, can beprepared according to the present invention by subjecting the2-substituted-2-cyclopentenones represented by the following formula(I-1): ##STR47## wherein R¹ and R²¹ are as defined above; A¹² and B aresuch that A¹² represents a hydroxyl group or ##STR48## and B representsa hydrogen atom or A¹² and B together represent a single bond; and R³⁰represents a substituted or non-substituted aliphatic hydrocarbon grouphaving 1 to 10 carbon atoms, when R³⁰ is a single bond and is bonded tothe cyclopentene skeleton, X⁰ represents a hydrogen atom, a hydroxylgroup or a protected hydroxyl group, and when R³⁰ is a double bond andbonded to the cyclopentene skeleton, X⁰ represents a bonding armconstituting a part of said double bond; l is 0 or 1; and j is 0, 1, or2; to oxidation reaction, and then to deprotection reaction and/orprotection reaction, if desired.

In the above formula (I-1), A¹² and B represent a combination in which Bis a hydrogen atom when A¹² is a hydroxyl group or ##STR49## or A¹² andB are mutually bonded together to represent one bonding arm. Specificexamples of A¹² and B include the same specific examples as mentionedabove for the above formula (I).

In the above formula (I-1), R¹ represents a substituted ornon-substituted hydrocarbon group having 1 to 10 carbon atoms. Specificexamples of R¹ include the same specific examples as mentioned above forthe above formula (I).

In the above formula (I-1), R²¹ represents an aliphatic hydrocarbongroup having 1 to 10 carbon atoms which may have as the substituent--COOR⁵¹ (where R⁵¹ represents a hydrogen atom, an alkyl group having 1to 10 carbon atoms or one equivalent cation); --OR⁶¹ (where R⁶¹ is anacyl group having 2 to 7 carbon atoms; a tri(C₁ -C₇)hydrocarbonsilylgroup; a group which forms an acetal bond together with the oxygen atomto which R⁶¹ is bonded; an aromatic hydrocarbon group which may besubstituted with a halogen atom, a tri(C₁ -C₇)hydrocarbonsilyloxy group,an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, analkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to4 carbon atoms); an aromatic hydrocarbon group which may be substitutedwith a halogen atom, a tri(C₁ -C₇)hydrocarbonsilyloxy group, an acyloxygroup having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbonatoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkylgroup having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4carbon atoms; or an alicyclic group which may be substituted with ahalogen atom, a tri(C₁ -C₇)hydrocarbonsilyloxy group, an acyloxy grouphaving 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, analkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms.Specific examples of R²¹ include the same specific examples as mentionedabove for R² in the above formula (I).

In the above formula (I-1), R³⁰ represents a substituted ornon-substituted aliphatic hydrocarbon group having 1 to 10 carbon atoms.Where R³⁰ is a single bond and bonded to the cyclopentene skeleton, X⁰represents a hydrogen atom, a hydroxyl group or a protected hydroxylgroup, and when R³⁰ is a double bond and bonded to the cyclopenteneskeleton, X⁰ represents a bond in said double bond. Specific examples ofR³⁰ and X³⁰ include the same specific examples as mentioned above for R³and X, respectively, in the above formula (I).

In the above formula (I-1), l represents 0 or 1 and j represents 0, 1 or2. In the process of the present invention, the2-substituted-2-cyclopentenones represented by the above by subjectingthe compound of the above formula (I-1) to and oxidation reaction, andfurther to a deprotection reaction and/or protection reaction, ifnecessary, formula (I-2) can be prepared. This oxidation reaction,deprotection reaction and/or protection reaction can be carried out bythe same method as used in the preparation of the2-substituted-2-cyclopentenones represented by the above formula(I-b-11) from the 2-substituted-2-cyclopentenones represented by theabove formula (I-b-10).

In the present invention, the preparation processes according to theembodiments as shown below are applicable.

1. A process for preparing the 2-substituted-2-cyclopentenonesrepresented by the following formula (I-b-11): ##STR50## wherein R¹ isas defined above;

As defined above, R² and R³⁴ are preferably aliphatic hydrocarbon groupshaving 1 to 10 carbon atoms which may have as the substitutent --COOR⁵(where R⁵ represents a hydrogen atom, an alkyl group having 1 to 10carbon atoms or one equivalent cation); --OR⁶ (where R⁶ is a hydrogenatom; an acyl group having 2 to 7 carbon atoms; a tri(C₁-C₇)hydrocarbonsilyl group; a group which forms an acetal bond togetherwith a oxygen atom to which R⁶ is bonded; an aromatic hydrocarbon groupwhich may be also substituted with a halogen atom, a hydroxyl group, atri(C₁ -C₇)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy grouphaving 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, analkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms); anaromatic hydrocarbon group which may be substituted with a halogen atom,a hydroxyl group, a tri(C₁ -C₇)hydrocarbonsilyloxy group, a carboxylgroup, an acyloxy group having 2 to 7 carbon atoms, an acyl group having2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms,an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1to 4 carbon atoms; or an alicyclic group which may be substituted with ahalogen atom, a hydroxyl group, a tri(C₁ -C₇)hydrocarbonsilyloxy group,a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acylgroup having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5carbon atoms, an alkyl group having 1 to 4 carbon atoms and an alkoxygroup having 1 to 4 carbon atoms; and n represents 0, 1 or 2, whichcomprises subjecting the 2-cyclopentenones represented by the followingformula (III-a): ##STR51## wherein R²¹ and R³¹ represent an aliphatichydrocarbon group having 1 to 10 carbon atoms which may have as thesubstituent --COOR⁵¹ (where R⁵¹ is an alkyl group having 1 to 10 carbonatoms); --OR⁶¹ (where R⁶¹ is an acyl group having 2 to 7 carbon atoms; atri(C₁ -C₇)hydrocarbonsilyl group; a group which forms an acetal bondtogether with a hydrogen atom to which R⁶¹ is bonded; an aromatichydrocarbon group may be also substituted with a halogen atom, a tri(C₁-C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbonatoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl grouphaving 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms,and an alkoxy group having 1 to 4 carbon atoms); an aromatic hydrocarbongroup which may be substituted with a halogen atom, a tri(C₁-C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbonatoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl grouphaving 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms,and an alkoxy group having 1 to 4 carbon atoms; or an alicyclic groupwhich may be substituted with a halogen atom, a tri(C₁-C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbonatoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl grouphaving 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atomsand an alkoxy group having 1 to 4 carbon atoms; to an epoxydizationreaction to obtain the 2,3-epoxycyclopentanones of the following formula(IV-a-1): ##STR52## wherein R²¹ and R³¹ are as defined above, thenreacting thiols represented by the following formula (V):

    R.sup.1 --SH                                               (V)

wherein R¹ represents a substituted or non-substituted hydrocarbon grouphaving 1 to 10 carbon atoms with said 2,3-epoxycyclopentanones in thepresence of a basic compound, alumina and/or silica gel, andsubsequently subjecting the reaction product, if necessary, to anoxidation reaction, deprotection reaction and/or protection reaction.

2. A process for preparing the 2-substituted-2-cyclopentenonesrepresented by the following formula (I-a-1): ##STR53## wherein R¹, R²,R³⁴, and n are as defined above; and the representation denotes that thesubstituent bonded to the double bond is in an E-configuration or aZ-configuration or mixtures thereof at any desired ratio which comprisesdehydrating the 2-substituted-2-cyclopentenones represented by thefollowing formula (I-b-10): ##STR54## wherein R¹, R²¹ and R³¹ are asdefined above, and subsequently subjecting the dehydrated product tooxidation reaction, deprotection reaction and/or protection reaction.

3. A process for preparing the 2-substituted-2-cyclopentenonesrepresented by the following formula (I-a-1): ##STR55## wherein R¹, R²,R³⁴, n and the representation are as defined above,

and the 2-substituted-2-cyclopentenones represented by the followingformula (I-b-12): ##STR56## wherein R¹, R², R³⁴, and n are as definedabove, and m represents 0, 1 or 2, which comprises allowing the2,3-epoxycyclopentanones represented by the following formula (IV-a-2):##STR57## wherein R²¹, R³¹ and the representation are as defined above,to react with thiols represented by the following formula (V):

    R.sup.1 --SH                                               (V)

wherein R¹ is as defined above, in the presence of a basic compound,alumina and/or silica gel, and then carrying out an oxidation reaction,deprotection reaction and/or protection reaction, if desired.

4. A process for preparing the 2-substituted-2-cyclopentenonesrepresented by the following formula (I-b-2): ##STR58## wherein R¹, R²,R³⁴ and n are as defined above; and R⁴ represents a hydrogen atom or aprotected group of the protected hydroxyl group, which comprisessubjecting the 2-substituted-2-cyclopentenones represented by thefollowing formula (III-b): ##STR59## wherein R³¹ represents an aliphatichydrocarbon group having 1 to 10 carbon atoms which may have as thesubstituent --COOR⁵¹ (where R⁵¹ is an alkyl group having 1 to 10 carbonatoms); --OR⁶¹ (where R⁶¹ is an acyl group having 2 to 7 carbon atoms; atri(C₁ -C₇)hydrocarbonsilyl group; a group which forms an acetal bondtogether with the oxygen atom to which R⁶¹ is bonded; an aromatichydrocarbon group which may be substituted with a halogen atom, a tri(C₁-C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbonatoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl grouphaving 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms,and an alkoxy group having 1 to 4 carbon atoms); an aromatic hydrocarbongroup which may be substituted with a halogen atom, a tri(C₁ -C.sub.7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbonatoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl grouphaving 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms,and an alkoxy group having 1 to 4 carbon atoms; or an alicyclic groupwhich may be substituted with a halogen atom, a tri(C₁-C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbonatoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl grouphaving 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atomsand an alkoxy group having 1 to 4 carbon atoms; and R⁴⁰ represents ahydrogen atom or a protected group of the protected hydroxyl group, toan epoxydization reaction to obtain the 2,3-epoxycyclopentanonesrepresented by the following formula (IV-b-1): ##STR60## wherein R³¹ R⁴⁰and are as defined above, then reacting the thiols represented by thefollowing formula (V):

    R.sup.1 --SH                                               (V)

wherein R¹ is as defined above, with the 2,3-epoxycyclopentanones in thepresence of a basic compound, alumina and/or silica gel, and furtherprotecting the hydroxyl group, if desired, to obtain the2-substituted-2-cyclopentenones represented by the following formula(I-c-1): ##STR61## wherein R¹ and R³¹ are as defined above; and R⁴¹represents a protected group of the protected hydroxyl group, andcarrying out an aldol condensation reaction which aldehydes representedby the following formula (II):

    OHC--R.sup.21                                              (II)

wherein R²¹ is as defined above, and subsequently, subjecting thereaction product to an oxidation reaction, deprotection reaction and/orprotection reaction, if desired.

5. A process for preparing the 2-substituted-2-cyclopentenonesrepresented by the following formula (I-a-2): ##STR62## wherein R¹, R²,R³⁴, R⁴, n and the representation are as defined above, which comprisesdehydrating the 2-substituted-2-cyclopentenones represented by thefollowing formula (I-b-20): ##STR63## wherein R¹, R²¹, R³¹ and R⁴¹ areas defined above, and subsequently subjecting the dehydrated product tooxidation reaction, deprotection reaction and/or protection reaction, ifdesired.

6. A process for preparing the 2-substituted-2-cyclopentenonesrepresented by the following formula (I-a-3'): ##STR64## wherein R¹, R²,n and the representation are as defined above; and R³³ represents ahydrogen atom or an aliphatic hydrocarbon group having 1 to 9 carbonatoms having as the substituent --COOR⁵ (where R⁵ represents hydrogenatom, an alkyl group having 1 to 10 carbon atoms or one equivalentcation); --OR⁶ (where R⁶ is an acyl group having 2 to 7 carbon atoms; atri(C₁ -C₇)hydrocarbonsilyl group; a group which forms an acetal bondtogether with the oxygen atom to which R⁶ is bonded; an aromatichydrocarbon group which may be substituted with a halogen atom, ahydroxyl group, a tri(C₁ -C₇)hydrocarbonsilyloxy group, a carboxylgroup, an acyloxy group having 2 to 7 carbon atoms, an acyl group having2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms,an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1to 4 carbon atoms); an aromatic hydrocarbon group which may besubstituted with a halogen atom, a hydroxyl group, a tri(C₁-C₇)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, analkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms; or analicyclic group which may be substituted with a halogen atom, a hydroxylgroup, a tri(C₁ -C₇)hydrocarbonsilyloxy group, a carboxyl group, anacyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, analkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4carbon atoms; which comprises subjecting the2-substituted-2-cyclopentenones represented by the formula (I-a-21):##STR65## wherein R¹, R²¹, R⁴, n and the representation are as definedabove; and R³² represents a hydrogen atom or an aliphatic hydrocarbongroup having 1 to 9 carbon atoms which may have as the substituent--COOR⁵¹ (where R⁵¹ is an alkyl group having 1 to 10 carbon atoms);--OR⁶¹ (where R⁶¹ is an acyl group having 2 to 7 carbon atoms; a tri(C₁-C₇)hydrocarbonsilyl group; a group which forms an acetal bond togetherwith the oxygen atom to which R⁶¹ is bonded; an aromatic hydrocarbongroup which may be substituted with a halogen atom, a tri(C₁-C₇)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbonatoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl grouphaving 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms,and an alkoxy group having 1 to 4 carbon atoms); an aromatic hydrocarbongroup which may be substituted with a halogen atom, a hydroxy group, atri(C₁ -C₇)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy grouphaving 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, analkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms; or analicyclic group which may be substituted with a halogen atom, a hydroxylgroup, a tri(C₁ -C₇)hydrocarbonsilyloxy group, a carboxyl group, anacyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, analkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4carbon atoms, and subsequently subjecting the reaction product tooxidation reaction, deprotection reaction and/or protection reaction, ifdesired.

7. A process for preparing the 2-substituted-2-cyclopentenonesrepresented by the following formula (I-2): ##STR66## wherein R¹, R², R³and X are as defined above; A¹¹ and B are such that A¹¹ represents ahydroxyl group or ##STR67## and B represents a hydrogen atom or A¹¹ andB together represent a single bond; k represents 1 to 2; and irepresents 0, 1 or 2, which comprises subjecting the2-substituted-2-cyclopentenones represented by the following formula(I-1): ##STR68## wherein R¹ and R²¹ are as defined above; A¹² and B aresuch that A¹² represents a hydroxyl group or ##STR69## and B representsa hydrogen atom or A¹² and B together represent a single bond, and R³⁰represents a substituted or non-substituted aliphatic hydrocarbon grouphaving 1 to 10 carbon atoms, when R³⁰ is a single bond and is bonded tothe cyclopentene skeleton, X⁰ represents a hydrogen atom, hydroxyl groupor a protected hydroxyl group, and when R³⁰ is a double bond and bondedto the cyclopentene skeleton, X⁰ represents a bonding arm constituting apart of said double bond; l represents 0 or 1; and j represents 0, 1, or2, to an oxidation reaction, and then to a deprotection reaction and/orprotection reaction, if desired.

8. A process for preparing 2-substituted-2-cyclopentenones according tothe above items 1 or 4, wherein the epoxydization reaction is carriedout by using hydrogen peroxide in the presence of an alkali metalhydroxide or carbonate.

9. A process for preparing 2-substituted-2-cyclopentenones according tothe above items 1, 3, 4 or 8, wherein the basic compound to be used inthe reaction with the thiols represented by the above formula (V) is analkali metal hydroxide or carbonate, or an amine.

10. A process for preparing 2-substituted-2-cyclopentenones according tothe above items 4, 8 or 9, wherein the aldol condensation reaction iscarried out in the presence of a basic compound anddibutylborontrifluoremethanesulfonic acid.

11. A process for preparing 2-substituted-2-cyclopentenones according tothe above items 4, 8 or 9, wherein the aldol condensation reaction iscarried out in the presence of lithium diisopropylamide.

12. A process for preparing 2-substituted-2-cyclopentenones according tothe above items 2 or 5, wherein the dehydration reaction of the aboveformula (I-b-10) or (I-b-20) is carried out by using a basic compoundand a reactive derivative of an organic sulfonic acid.

13. A process for preparing 2-substituted-2-cyclopentenones according tothe above items 1 to 12, wherein the oxidation reaction is carried outby using an organic peracid.

14. A process for preparing 2-substituted-2-cyclopentenones according tothe above items 1 to 12, wherein the oxidation reaction is carried outby using an organic periodic acid salt.

The compound according to the present invention can be administered byoral, subcutaneous, intramuscular, intravenous, intraarterial, andsuppository administration, etc., methods.

Solid preparations or liquid preparations can be formed for oraladministration, and include, for example, tablets, pills, powders,granules, solutions, suspensions or capsules. When preparing tablets bya conventional method, excipients such as lactose, starch, calciumcarbonate, crystalline cellulose or silicic acid; binders such ascarboxymethyl cellulose, methyl cellulose, calcium phosphate orpolyvinyl pyrrolidone; disintegrating agents such as sodium alginate,sodium hydrogen carbonate, sodium lauryl sulfate or stearic acidmonoglyceride; humectants such as glycerine; absorbers such as kaolin,and colloidal silica; and lubricants such as talc and granular boricacid may be employed.

Pills, powders or granules also can be prepared by conventional methodsusing the same additives as mentioned above.

Liquid preparations such as solutions and suspensions also can beprepared by conventional methods. As the carrier, for example, glycerolesters such as tricaprin, triacetin, iodated poppy seed oil fatty acidesters; water; alcohols such as ethanol; and oily bases such as fluidparaffin, coconut oil, soybean oil, sesame oil, and corn oil may beemployed.

The powders, granules, liquid preparations as described above also canbe enclosed within capsules of, for example, gelatin.

The pharmaceutically acceptable carrier in the present specificationalso includes other auxiliary agents, aromatic agents, stabilizers orpreservatives conventionally used as optional components.

The preparation for parental administration may be a sterile aqueous ornonaqueous solution, suspension or emulsion. The nonaqueous solution orsuspension may employ propylene glycol and polyethylene glycol, or avegetable oil such as olive oil, an injectable organic ester such asethyl oleate, and iodated poppy seed fatty acid esters as the carrier.The preparation also can contain auxiliary agents such as preservatives,humectants, emulsifiers, dispersing agents, and stabilizers. Thesesolutions, suspensions and emulsions can be sterilized by a treatmentsuch as filtration through bacteria-retaining filter, formulation with asterilizer, or irradiation. It is also possible to prepare a sterilesolid preparation, which is dissolved in sterile water or a sterilesolvent for injection immediately before use.

The compounds of the present invention also can be used by forminginclusion compounds together with α, β or γ-cyclodextrin or methylatedcyclodextrin, and may be injectable preparations in the lipogenatedform.

The effective dose of the compounds of the present invention depends onthe age, sex, and condition of the patient, but generally may beadministered at 10² to 10⁵ μg/Kg/day, preferably 5×10² to 10⁴ μg/Kg/day.

The 2-substituted-2-cyclopentenones of the present invention have apotent growth inhibitory effect against L1210 leukemia cells even at alow concentration, are useful as antitumor agents.

Furthermore, the present compounds have the activities of enhancing thealkali phosphatase activity of human osteoblast, and further, enhancingthe calcium and phosphorus contents in osteoblast. Accordingly, thepresent compounds are also useful as a bone formation accelerator, andare effective for the therapy or prophylaxis of osteoporosis orosteomalacia.

Furthermore, the present compounds are expected to exhibit an antiviralactivity or antibacterial activity and are very useful components as thepharmaceutical products.

EXAMPLES

The present invention is described in detail below with reference toExamples.

EXAMPLE 1 Synthesis of2,3-epoxy-5-(1-hydroxy-6-methoxycarbonylhexyl-4-(3-t-butyldimethylsilyloxy-1-octenyl)cyclopentanone##STR70##

A solution of 3.30 g of5-(1-hydroxy-6-methoxycarbonylhexyl)-4-(3-t-butyldimethylsilyloxy-1-octenyl)-2-cyclopentenonein methanol (25 ml) was cooled to 0° C., and 48 ml of an aqueous 30%hydrogen peroxide and 0.48 ml of an aqueous 1N sodium hydroxide weredropwise added thereto. After stirring at 0° C. for 3 hours, thereaction mixture was extracted with an addition of ethyl acetate andsaturated aqueous ammonium chloride, and the extract was washed withsaturated aqueous sodium chloride, dried over anhydrous magnesiumsulfate and filtered, followed by concentration. The concentrate wassubjected to silica gel chromatography to give 2.54 g (yield 74%) of2,3-epoxy-5-(1-hydroxy-6-methoxycarbonylhexyl)-4-(3-t-butyldimethylsilyloxy-1-octenyl)cyclopentanone.

Spectrum data

¹ H-HMR CDCl₃ δ

-0.03 (3H, s), 0.00 (3H, s), 0.84 (9H, s), 0.7-1.1

(3H, brt), 1.1-2.3 (20H, m), 3.4-3.5 (1H,m),

3.61 (3H, s), 3.68 (1H, brs), 4.0-4.1 (1H,m),

5.5-5.7 (2H, m)

EXAMPLES 2 TO 5

The 2,3-epoxycyclopentanones listed in Table 1 were obtained in the samemanner as in Example 1.

    TABLE 1      Example No. Starting compound 2-cyclopentanones 2,3-epoxy cyclopentanone     s Yield (%) NMR (δ      CDCl.sub.3)                                            2      ##STR71##      ##STR72##      51 0.00(3H, s), 0.05(3H, s), 0.89(9H, s),1.2-2.0(11H, m),2.0-2.6(5H,     m), 3.1-3.3(1H, m), 3.50(1H, d,J=2.5Hz), 3.69(3H, s), 3.77(1H, d,J=2.5Hz)     , 3.8-4.05(1H, m), 4.4-4.9(2H, m), 5.3-5.9(2H, m)       3     ##STR73##      ##STR74##      63 0.01(3H, s), 0.06(3H, s), 0.89(9H, s),0.7-1.1(6H, m), 1.1-2.7(17H,     m), 3.0-3.3(1H, m), 3.49(1H, d,J=2.5Hz), 3.68(3H, s), 3.79(1H, d,J=2.5Hz)     , 3.6-4.6(2H, m), 5.4-5.9(2H, m), 5.87(1H, d,J=16.0Hz), 7.03(1H,dt,     J=16.0, 7.2Hz)      4     ##STR75##      ##STR76##      43 1.1-2.7(29H, m),2.9-3.3(1H, m), 3.3-4.4(5H, m), 3.69(3H, s),4.5-5.0(2     H, m), 5.3-5.8(2H, m)      5     ##STR77##      ##STR78##      69 0.7-1.1(3H, m), 1.1-3.1(9H, m), 3.3-3.6(1H, m), 3.49(1H, d,J=2.6Hz),     3.76(1H, d,J=2.6Hz), 4.3-4.7(1H, m), 6.4-6.8(1H, m), 7.0-8.0(5H,     m)

EXAMPLE 6 Synthesis of2-methylthio-5-(l-hydroxy-6-methoxycarbonylhexyl)-4-(3-t-butyldimethylsilyloxy-1-octenyl)-2-cyclopentenone##STR79##

A solution of sodium thiomethoxide (2.30 g) in methanol (100 ml) wascooled to 0° C., acetic acid (2.82 ml) was added, the mixture wasstirred for 5 minutes, Triethylamine (915 ml) was added, and a solutionof2,3-epoxy-5-(1-hydroxy-6-methoxycarbonylhexyl)-4-(3-t-butyldimethylsilyloxy-1-octenyl)cyclopentanone(3.26 g) in methanol (40 ml) was added. After stirring at roomtemperature for 12 hours, water was added to the mixture, and themixture extracted with ethyl acetate. The extract was washed with asaturated aqueous sodium chloride solution, dried over anhydrousmagnesium sulfate and filtered, followed by concentration. Theconcentrate was subjected to silica gel chromatography to give 3.47 g(yield 96%) of2-methylthio-5-(1-hydroxy-6-methoxycarbonylhexyl)-4-(3-t-butyldimethylsilyloxy-1-octenyl)-2-cyclopentenone.

Spectrum data

¹ H-NMR CDCl₃ δ

0.00 (3H, s), 0.03 (3H, s), 0.87 (9H, s),

0.7-1.1 (3H, brt), 1.1-2.3 (20H, m), 2.33

(3H, s), 3.1-3.3 (1H, m), 3.63 (3H, s),

3.6-3.8 (1H, brs), 3.9-4.2 (1H, m), 5.4-5.6

(2H, m), 6.78 (1H, d, J=3 Hz).

EXAMPLES 7-9

The 2-substituted-2-cyclopentenes listed in Table 2 were obtained in thesame manner as in Example 6.

    TABLE 2      Example No. Starting compound 2-Substituted-2-cyclopentenones Yield (%) N     MR (δ      CDCl.sub.3)                                                         7      ##STR80##      ##STR81##      54 0.04(6H, s), 0.89(9H, s), 1.1-2.1(11H, m), 2.1-3.1(6H, m), 2.32(3H,     s),3.1-3.5(1H, m), 3.68(3H, s), 3.8-4.0(1H, m), 4.6-4.85(1H, m),     5.3-5.9(2H, m), 6.90(1H, d,J=3.0Hz)      8     ##STR82##      ##STR83##      60 0.01(3H, s), 0.04(3H, s), 0.89(9H, s),0.7-1.1(6H, m), 1.1-2.7(17H,     m), 2.33(3H, s),3.1-3.3(1H, m), 3.68(3H, s), 3.6-3.9(3H, m), 3.8-4.3(1H,     m), 5.4-5.8(2H, m), 5.89(1H, d,J=16.0Hz), 6.82(1H,d, J=2.5Hz), 7.02(1H,     dt, J=16.0, 7.4Hz)      9     ##STR84##      ##STR85##      72 0.7-1.1(3H, m), 1.1-3.3(9H, m), 2.34(3H, s),3.3-3.6(1H, m), 4.3-4.7(1     H, m), 6.4-6.9(2H, m), 7.0-8.0(5H, m)

EXAMPLE 10 Synthesis of2-(2,3-dihydroxypropylthio)-5-(1-hydroxy-6-methoxycarbonyl-2-hexynyl)-4-(3-t-butyldimethylsilyloxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone##STR86##

A 49 mg amount of2,3-epoxy-5-(1-hydroxy-6-methoxycarbonyl-2-hexynyl)-4-(3-t-butyldimethylsilyloxy-3-cyclopentyl-1-propenyl)cyclopentanonewas dissolved in 1 ml of methanol and 21 μl of triethylamine was added.Then, 12 mg of 2,3-dihydroxypropanethiol was added thereto, followed bystirring for 2 hours. The reaction mixture was poured on an aqueoussaturated solution of potassium hydrogen sulfate, followed by extractingwith ethyl acetate. The extracted solution was washed with a saturatedsodium chloride solution and dried over anhydrous magnesium sulfate.After filtering and concentrating, the concentrate was subjected tosilica gel chromatography to give 36 mg (yield 62%) of2-(2,3-dihydroxypropylthio)-5-(1-hydroxy-6-methoxycarbonyl-2-hexynyl)-4-(3-t-butyldimethylsilyloxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone.

Spectrum data

¹ H-NMR CDCl₃ δ

0.05 (3H, s), 0.09 (3H, s), 0.89 (9H, s),

1.1-2.0 (11H, m), 2.0-2.7 (5H, m), 2.7-3.4

(6H, m), 3.67 (3H, s), 3.4-4.0 (4H, m),

4.5-4.9 (1H, m), 5.4-5.8 (2H, m), 7.1-7.3

(1H, m)

EXAMPLES 11-18

The 2-substituted-2-cyclopentenes listed in Table 3 were obtained in thesame manner as in Example 10.

    TABLE 3      Ex-     am- ple Starting compound 2-Substituted-2-cyclo- Yield NMR No.     2,3-epoxycyclopentanones Thiols pentenones (%) (δCDCl.sub.3)             11      ##STR87##      ##STR88##      ##STR89##      71 0.04(6H, s), 0.89(9H, s), 1.1-2.1(17H, m), 2.1-3.1(10H, m), 3.4-3.8(1     H, m), 3.67(6H, s), 3.8-4.0(1H, m), 4.6-4.85(1H, m), 5.4-5.8(2H, m),     6.92(1H,d, J= 3.2 Hz)  2,3-epoxy-5-(1-hydroxy-6- 5-methoxycarbonyl-     2-(5-methoxycarbonylpen-  methoxycarbonyl-2-hexynyl)-4- pentane-1-thiol     tylthio)-5-(1-hydroxy-6-  (3-t-butyldimethylsilyloxy-3-  methoxycarbonyl-     2-hexynyl)-4-  cyclopentyl-1-propenyl)cyclo-  (3-t-butyldimethylsilyloxy-     3-  pentanone  cyclopentyl-1-propenyl)-2-    cyclopentenone  12      ##STR90##      ##STR91##      74 0.04(6H, s), 0.90(9H, s), 1.0-3.0(23H, m), 3.35-3.7(1H, m), 3.68(3H,     s), 3.8-4.0(1H, m), 4.6-4.8(1H, m), 5.4-5.7(2H, m), 6.89(1H,d, J= 2.8     Hz),7.0-7.4(5H, m)   3-phenylpropane-1- 2-(3-phenylpropylthio)-5-(1-     thiol hydroxy-6-methoxycarbonyl-2-    hexynyl)-4-(3-t-butyldimethyl-     silyloxy-3-cyclopentyl-1-    propenyl)-2-cyclopentenone      13     ##STR92##      ##STR93##      91 0.07(6H, s), 0.89(9H, s), 1.1-2.0(11H, m), 2.0-2.7(5H, m), 3.0-3.3(1H     , m), 3.4-3.6(1H, m), 3.70(3H, s), 3.8-4.0(1H, m), 4.7-4.9(1H, m),     5.4-5.8(2H, m), 6.85(1H,d, J= 2.7 Hz),7.2-7.7(5H, m)   Thiophenol     2-phenylthio-5-(1-hydroxy-6-    methoxycarbonyl-2-hexynyl)-4-     (3-t-butyldimethylsilyloxy-3-    cyclopentyl-1-propenyl)-2-    cyclopente     none      14     ##STR94##      ##STR95##      85 0.08(6H, s), 0.89(9H, s), 1.1-2.0(11H, m),2.0-2.7(5H, m),3.3-3.5(1H,     m),3.69(3H, s),3.8-4.1(2H, m),3.97(3H, s),4.6-4.8(1H, m),5.4-5.8(2H,     m),6.74(1H, d,J= 2.7 Hz),7.0-8.1(6H, m)   6-methoxynaphtha- 2-(6-methoxyn     aphthyl-2-thio)-   lene-2-thiol 5-(1-hydroxy-6-methoxy-    carbonyl-2-hex     ynyl)-4-(3-t-    butyldimethylsilyloxy-3-cyclo-    pentyl-1-propenyl)-2-c     yclo-    pentenone      15     ##STR96##      CH.sub.3 CH.sub.2      SH     ##STR97##      75 0.04(3H, s), 0.09(3H, s), 0.89(9H, s), 0.7-1.1(6H, m), 1.1-2.7(22H,     m), 3.1-3.3(1H, m), 3.68(3H, s), 3.6-3.8(1H, brs), 3.9-4.2(1H, m),     5.3-5.7(2H, m), 6.79(1H,d, J= 2.9 Hz)  2,3-epoxy-5-(1-hydroxy-6-     ethanethiol 2-ethylthio-5-(1-hydroxy-6-  methoxycarbonylhexyl)-4-(3-t-     methoxycarbonylhexyl)-4-(3-t-  butyldimethylsilyloxy-1-  butyldimethylsil     yloxy-1-  octenyl)cyclopentanone  octenyl)-2-cyclopentenone      16     ##STR98##      ##STR99##      ##STR100##      62 0.01(3H, s), 0.05(3H, s), 0.89(9H, s), 0.7-1.1(6H, m), 1.1-2.7(17H,     m), 3.1-3.3(1H, m), 3.69(3H, s), 3.6-3.9(3H, m), 3.9-4.3(1H, m),     5.3-5.9(2H, m), 5.88(1H,d, J= 16.0 Hz),6.85(1H, d,J= 2.7 Hz), 7.04(1H,     dt, J= 16.0,7.2 Hz), 7.26(4H, s)  2,3-epoxy-5-(1-hydroxy-6- 4-chloropheny     l- 2-(4-chlorophenylmethylthio)-  methoxycarbonyl-5-hexenyl)- methanethio     l 5-(1-hydroxy-6-methoxy-  4-(3-t-butyldimethylsilyloxy-  carbonyl-5-hexe     nyl)-4-(3-t-  5-methyl-1-nonenyl)cyclo-  butyldimethylsilyloxy-5-     pentanone  methyl-1-nonenyl)-2-cyclo-    pentenone      17     ##STR101##      CH.sub.3 CH.sub.2      SH     ##STR102##      57  0.7-1.1(3H, m),1.1-2.7(31H, m),3.0-3.3(1H, m),3.69(3H, s),3.3-4.3(3H     , m),4.5-5.0(2H, m),5.3-5.7(2H, m),6.80(1H, d,J= 2.8 Hz)  2,3-epoxy-5-(1-     hydroxy-6- ethanethiol 2-ethylthio-5-(1-hydroxy-6-  methoxycarbonylhexyl)     -4-[3-  methoxycarbonylhexyl)-4-[3-  (tetrahydropyran-2-yloxy)-3-     (tetrahydropyran-2-yloxy)-3-  cyclohexyl-1-propenyl]cyclo-  cyclohexyl-1-     propenyl]-2-  pentanone  cyclopentenone      18     ##STR103##      ##STR104##      ##STR105##      82 0.7-1.1(3H, m),1.1-3.3(9H, m),2.30(3H, s),3.3-3.6(1H, m),4.3-4.7(1H,     m),6.4-6.9(2H, m),6.9-8.0(9H, m)  2,3-epoxy-5-(1-hydroxy-3- 4-methylbenze     ne- 2-(4-methylphenylthio)-5-(1-  phenyl-2-propenyl)-4-butyl- thiol     hydroxy-3-phenyl-2-propenyl)-  cyclopentanone  4-butyl-2-cyclopentenone

EXAMPLE 19 Syntheses of5-(6-methoxycarbonyl-1-methylthiohexyl)-2-methylthio-4-(1-octenyl)-2-cyclopentenoneand5-(6-methoxycarbonylhexylidene)-2-methylthio-4-(1-octenyl)-2-cyclopentenone##STR106##

To a solution of 16.9 mg of sodium thiomethoxide dissolved in 1 ml ofmethanol, 39 μl of acetic acid was added under ice-cooling and stirring.A solution of 60 mg of2,3-epoxy-4-(1-octenyl)-5-(6-methoxycarbonylhexylidene)cyclopentanone in1 ml of methanol was added, then triethylamine (144 μl ) was added, andthe mixture was stirred at 0° C. for 4 hours. The reaction mixture wasdiluted with saturated aqueous ammonium chloride and extracted withethyl acetate. The organic layer was washed with saturated aqueoussodium chloride, dried over anhydrous magnesium sulfate, filtered,concentrated and then provided for silica gel column chromatography togive 16.7 mg (yield 20%) of5-(6-methoxycarbonyl-1-methylthiohexyl)-2-methylthio-4-(1-octenyl)-2-cyclopentenoneand 9.0 mg (yield 13%) of5-(6-methoxycarbonylhexyl)-2-methylthio-4-(1-octenyl)-2-cyclopentenone.

Spectrum data

(A) 1H-NMR (CDCl₃) δ

0.89 (3H, brt, J=5.5 Hz), 1.0-2.5 (20H, m),

2.37 (3H, s), 3.68 (3H, s), 3.96 (1H, brd,

J=4.0 Hz), 4.20 (1H, dd, J=15.0, 8.5 Hz),

4.67 (1H, dt, J=15.0, 6.4 Hz), 6.5-6.8

(2H, m).

(B) 1H-NMR (CDCl₃) δ

0.89 (3H, brt, J=5.0 Hz), 1.1-1.9 (16H, m),

2.06 and 2.08 (3H, s), 1.9-2.7 (5H, m), 2.37

(3H, s), 3.0-3.3 (1H, m), 3.4-3.6 (1H, m),

3.69 (3H, s), 5.36 (1H, dd, J=15.5, 7.8 Hz),

5.61 (1H, dt, J=15.5, 7.8 Hz), 6.87 and 6.90

(1H, d, J=3.0 Hz).

EXAMPLE 20 Synthesis of2-methylthio-5-(1-hydroxy-6-methoxycarbonylhexyl)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone##STR107##

To 350 mg of2-methylthio-5-(1-hydroxy-6-methoxycarbonylhexyl)-4-(3-t-butyldimethylsilyloxy-1-octenyl)-2-cyclopentenoneobtained in Example 6 was added a solvent mixture of 10 ml of aceticacid, 5 ml of tetrahydrofuran, and 5 ml of water, and the mixture wasstirred for 24 hours. Toluene was then added, and after concentration,the concentrate was diluted with saturated aqueous sodiumhydrogencarbonate and extracted with ethyl acetate. Subsequently, theextract was washed with saturated aqueous sodium chloride, dried overanhydrous magnesium sulfate, filtered and concentrated, followed bysilica gel chromatography to give 178 mg (yield 65%) of2-methylthio-5-(1-methoxycarbonylhexyl)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone.

Spectrum data

¹ H-NMR CDCl₃ δ

0.89 (3H, brt), 1.1-2.4 (21H, m), 2.34

(3H, s), 3.1-3.4 (1H, m), 3.65 (3H, s),

3.6-3.9 (1H, m), 3.9-4.2 (1H, m), 5.2-5.9

(2H, m), 6.79 (1H, d, J=3 Hz).

EXAMPLE 21 Synthesis of2-methylsulfinyl-5-(1-hydroxy-6-methoxycarbonylhexyl)-4-(3-hydroxy-1-octenyl)-2-cyclopetenone##STR108##

To a solution of 35 mg of2-methylthio-5-(1-hydroxy-6-methoxycarbonylhexyl)-4-(3-hydroxy-1-octenyl)-2-cyclopentenoneobtained in Example 20 dissolved in 5 ml of dichloromethane was added 17mg of 3-chloroperbenzoic acid, and the mixture was stirred for 1 hour.Saturated aqueous sodium hydrogencarbonate was added, and the mixturewas extracted with ethyl acetate. An organic layer was added, and themixture was washed with saturated aqueous sodium chloride, dried overanhydrous sodium sulfate, filtered and concentrated, followed by silicagel chromatography to give 7.3 mg (yield 21%) of2-methylsulfinyl-5-(1-hydroxy-6-methoxycarbonylhexyl)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone.

Spectrum data

¹ H-NMR CDCl₃ δ

0.88 (3H, brt, J=5.7 Hz), 1.1-2.4 (21H, m),

2.34 (3H, s), 3.1-3.5 (1H, m), 3.66 (3H, s),

3.7-4.1 (1H, m), 3.9-4.2 (1H, m), 5.2-5.9

(2H, m), 7.80 (1H, d, J=3 Hz).

EXAMPLE 22 Synthesis of2-methylthio-5-(6-methoxycarbonylhexylidene)-4-(3-t-butyldimethylsilyloxy-1-octenyl)-2-cyclopentenone##STR109##

To a solution of 3.47 g of2-methylthio-5-(1-hydroxy-6-methoxycarbonylhexyl)-4-(3-t-butyldimethylsilyloxy-1-octenyl)-2-cyclopentenoneobtained in Example 6 in dichloromethane (30 ml) was addeddimethylaminopyridine (1.54 g) and the mixture was cooled to 0° C. Tothe solution was dropwise added 0.59 ml of methanesulfonyl chloride, andthe mixture was stirred at room temperature for 15 hours. To thereaction mixture were added ethyl acetate and an aqueous potassiumhydrogensulfate, and the product was extracted into an organic layer.The extract was washed with saturated aqueous sodium hydrogencarbonateand saturated sodium chloride, dried over anhydrous magnesium sulfate,and filtered, followed by concentration. The concentrate was subjectedto silica gel chromatography to give 2.15 g (yield 64%) of2-methylthio-5-(6-methoxycarbonylhexylidene)-4-(3-t-butyldimethylsilyloxy-1-octenyl)-2-cyclopentenone.

Spectrum data

¹ H-NMR CDCl₃ δ

0.00 (3H, s), 0.02 (3H, s), 0.87 (9H, s),

0.7-1.1 (3H, brt), 1.1-2.3 (18H, m), 2.33

(3H, s), 3.65 (3H, s), 3.9-4.1 (2H, m), 5.38

(1H, dd, J=7.5 Hz), 5.65 (1H, dd, J=15,

6 Hz, 6.5-6.8 (2H, m).

EXAMPLES 23-33

2-Substituted-2-cyclopentenones listed in Table 4 were obtained in thesame manner as in Example 12.

    TABLE 4        2-Substituted-2- Yield NMR Example No. Starting compound cyclopentanon     es (%) (δCDCl.sub.3)            23      ##STR110##      ##STR111##      33 0.00(3H, s), 0.03(3H, s), 0.88(9H, s), 0.7-1.1(6H, m), 1.1-2.7(20H,     m), 3.69(3H, s),3.9-4.1(2H, m), 5.3-5.8(2H, m), 6.5-6.9(2H, m)  2-ethylth     io-5-(1-hydroxy-6- 2-ethylthio-5-(6-methoxy-  methoxycarbonylhexyl)-4-(3-      carbonylhexylidene)-4-(3-t-  t-butyldimethylsilyloxy-1- butyldimethylsil     yloxy-1-  octenyl)-2-cyclopentenone octenyl)-2-cyclopentenone  24      ##STR112##      ##STR113##      23 0.01(3H, s), 0.03(3H, s), 0.89(9H, s),1.1-2.0(11H, m), 2.0-3.0(4H,     m), 2.34(3H, s),3.68(3H, s), 3.8-4.1(2H, m), 5.3-5.8(2H, m),6.5-6.9(2H,     m)  2-methylthio-5-(1-hydroxy-6- 2-methylthio-5-(6-methoxy-  methoxycarbo     nyl)-2-hexynyl)- carbonyl-2-hexynylidene)-4-(3-  4-(3-t-butyldimethylsily     loxy-3- t-butyldimethylsilyloxy-3-  cyclopentyl-1-propenyl)-2- cyclopenty     l-1-propenyl)-2-  cyclopentenone cyclopentenone      25     ##STR114##      ##STR115##      35 0.01-0.04(6H, m),0.89(9H, s), 1.1-2.1(17H, m), 2.1-3.1(8H, m),     3.69(6H, s), 3.8-4.1(2H, m), 5.3-5.8(2H, m), 6.5-6.9(2H, m)  2-(5-methoxy     carbonylpentyl- 2(5-methoxycarbonylpentyl-  thio)-5-(1-hydroxy-6-methoxy-      thio)-5-(6-methoxycarbonyl-2-  carbonyl-2-hexynyl)-4-(3-t- hexynylidene)     -4-(3-t-butyldi-  butyldimethylsilyloxy-3-cyclo- methylsilyloxy-3-cyclope     ntyl-  pentyl-1-propenyl)-2-cyclopen- 1-propenyl)-2-cyclopentenone     tenone      26     ##STR116##      ##STR117##      29 0.04(6H, s), 0.90(9H, s), 1.0-3.0(21H, m), 3.69(3H, s), 3.8-4.1(2H,     m), 5.3-5.8(2H, m), 6.5-6.9(2H, m), 7.0-7.4(5H, m)  2-(3-phenylpropylthio     )-5-(1- 2-(3-phenylpropylthio)-5-(6-  hydroxy-6-methoxycarbonyl-2-     methoxycarbonyl-2-hexynyli-  hexynyl)-4-(3-t-butyldimethyl- dene)-4-(3-t-     butyldimethyl-  silyloxy-3-cyclopentyl-1- silyloxy-3-cyclopentyl-1-     propenyl)-2-cyclopentenone propenyl)-2-cyclopentenone      27     ##STR118##      ##STR119##      24 0.05(6H, s), 0.89(9H, s), 1.1-2.1(11H, m), 2.1-2.6(4H, m), 3.68(3H,     s), 3.7-4.2(2H, m), 5.4-5.9(2H, m), 6.5-6.9(2H, m), 7.0-7.7(5H, m)     2-phenylthio-5-(1-hydroxy-6- 2-phenylthio-5-(6-methoxy-  methoxycarbonyl-     2-hexynyl)-4- carbonyl-2-hexylidene)-4-  (3-t-butyldimethylsilyloxy-3-     (3-t-butyldimethylsilyloxy-3-  cyclopentyl-1-propenyl)-2- cyclopentyl-1-p     ropenyl)-2-  cyclopentenone cyclopentenone      28     ##STR120##      ##STR121##       21 0.08(6H, s), 0.89(9H, s), 1.1-2.1(11H, m), 2.1-2.6(4H, m), 3.69(3H,     s),3.7-4.2(2H, m), 3.97(3H, s), 5.4-5.8(2H, m),6.5-6.9(2H, m),7.0-8.1(6H,      m)  2-(6-methoxynaphthyl-2-thio)- 2-(6-methoxynaphthyl-2-thio)-     5-(1-hydroxy-6-methoxy- 5-(6-methoxycarbonyl-2-  carbonyl-2-hexynyl)-4-(3     -t- hexynylidene)-4-(3-t-butyl-  butyldimethylsilyloxy-3-cyclo- dimethyls     ilyloxy-3-cyclo-  pentyl-1-propenyl)-2-cyclo- pentyl-1-propenyl)-2-cyclo-       pentenone pentenone      29     ##STR122##      ##STR123##      41 0.01-0.05(6H, m),0.89(9H, s), 0.7-1.0(6H, m), 1.0-1.9(11H, m),     1.9-2.5(4H, m), 2.35(3H, s),3.70(3H, s), 3.8-4.4(2H, m), 5.1-6.0(3H, m),     6.5-7.3(3H, m)  2-methylthio-5-(1-hydroxy-6- 2-methylthio-5-(6-methoxy-     methoxycarbonyl-5-hexenyl)-4- carbonyl-5-hexynylidene)-4-  (3-t-butyldime     thylsilyloxy-5- (3-t-butyldimethylsilyloxy-5-  methyl-1-nonenyl)-2-cyclo-      methyl-1-nonenyl)-2-cyclo-  pentenone pentenone      30     ##STR124##      ##STR125##      39 0.01(3H, s), 0.04(3H, s), 0.89(9H, s), 0.7-1.0(6H, m), 1.0-2.7(15H,     m), 3.68(3H, s), 3.6-3.9(4H, m), 5.3-6.1(3H, m), 6.5-7.4(7H, m)     2-(4-chlorophenylmethylthio)- 2-(4-chlorophenylmethylthio)-  5-(1-hydroxy     -6-methoxycarbony- 5-(6-methoxycarbonyl-5-  l-5-hexenyl)-4-(3-t-butyldi-     hexenylidene)-4-(3-t-butyldi-  methylsilyloxy-5-methyl-1- methylsilyloxy-     5-methyl-1-  nonenyl)-2-cyclopentenone nonenyl)-2-cyclopentenone  31      ##STR126##      ##STR127##      39 0.7-1.1(3H, m),1.1-2.7(29H, m),3.68(3H, s), 3.6-4.0(3H, m), 4.5-5.1(2     H, m), 5.3-5.8(2H, m), 6.5-7.0(2H, m)  2-ethylthio-5-(1-hydroxy-6-     2-ethylthio-5-(6-methoxy-  methoxycarbonylhexyl)-4-[3- carbonylhexylidene     )-4-[3-  (tetrahydropyran-2-yloxy)-3- (tetrahydropyran-2-yloxy)-3-     cyclohexyl-1-propenyl]-2- cyclohexyl-1-propenyl]-2-  cyclopentenone     cyclopentenone      32     ##STR128##      ##STR129##      63 0.7-1.0(3H, m),1.1-1.9(6H, m), 2.33(3H, s), 3.3-3.8(1H, m), 6.0-7.7(9     H, m)  2-methylthio-5-(1-hydroxy-3- 2-methylthio-5-(3-phenyl-2-     phenyl-2-propenyl)-4-butyl-2- propenylidene)-4-butyl-2-  cyclopentenone     cyclopentenone      33     ##STR130##      ##STR131##      57 0.7-1.0(3H, m),1.1-1.9(6H, m), 2.30(3H, s), 3.3-3.8(1H, m), 6.0-7.9(1     3H, m)  2-(4-methylphenylthio)-5-(1- 2-(4-methylphenylthio)-5-(3-     hydroxy-3-phenyl-2-propenyl)- phenyl-2-propenylidene)-4-  4-butyl-2-cyclo     pentenone butyl-2-cyclopentenone

EXAMPLE 34 Synthesis of2-methylthio-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone##STR132##

An amount of 1.42 g of2-methylthio-5-(6-methoxycarbonylhexylidene-4-(3-t-butyldimethylsilyloxy-1-octenyl)-2-cyclopentenoneobtained in Example 22 was added to a mixture of acetic acid (2.1 ml),tetrahydrofuran (1.4 ml) and water (0.7 ml), and the mixture was stirredat room temperature for 2 days. To the reaction mixture saturatedaqueous sodium hydrogencarbonate and ethyl acetate were added, and theproduct was extracted into the organic layer. The extract was washedwith saturated aqueous sodium chloride, then dried over anhydrousmagnesium sulfate and filtered, followed by concentration. Theconcentrate was subjected to silica gel chromatography to give 0.93 g(yield 85%) of2-methylthio-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone.

Spectrum data

¹ H-NMR CDCl₃ δ

0.89 (3H, brt), 1.1-2.4 (19H, m), 2.35

(3H, s), 3.66 (3H, s), 3.9-4.2 (2H, m),

5.2-5.9 (2H, m), 6.6-6.8 (2H, m).

EXAMPLES 35-44

2-Substituted-2-cyclopentenones listed in Table 5 were obtained in thesame manner as in Example 34.

    TABLE 5      Example  2-Substituted-2- Yield NMR No. Starting compound cyclopentanone     s (%) (δCDCl.sub.3)            36      ##STR133##      ##STR134##      77 0.7-1.1(6H, m),1.1-2.7(21H, m),3.69(3H, s), 3.9-4.1(2H, m), 5.3-5.8(2     H, m), 6.5-6.9(2H, m)      37     ##STR135##      ##STR136##      62 1.1-2.0(11H, m),2.0-3.0(5H, m), 2.35(3H, s), 3.67(3H, s), 3.8-4.1(2H,      m), 5.3-5.8(2H, m), 6.5-6.9(2H, m)      38     ##STR137##      ##STR138##      60 1.1-2.1(17H, m),2.1-3.1(9H, m), 3.69(6H, s), 3.8-4.1(2H, m),     5.3-5.8(2H, m), 6.5-6.9(2H, m)      39     ##STR139##      ##STR140##      71 1.0-3.0(22H, m),3.68(3H, s), 3.8-4.2(2H, m), 5.3-5.8(2H, m),     6.5-6.9(2H, m), 7.0-7.4(5H, m)      40     ##STR141##      ##STR142##      58 1.1-2.1(11H, m),2.1-2.9(5H, m), 3.68(3H, s), 3.7-4.2(2H, m),     5.4-5.9(2H, m), 6.5-6.97.0-7.7(5H, m)      41     ##STR143##      ##STR144##      64 1.1-2.1(11H, m),2.1-2.8(5H, m), 3.69(3H, s), 3.7-4.2(2H, m),     3.98(3H, s), 5.4-5.8(2H, m), 6.5-6.9(2H, m), 7.0-8.1(6H, m)      42     ##STR145##      ##STR146##      69 0.7-1.0(6H, m),1.0-1.9(11H, m),1.9-2.8(5H, m), 2.33(3H, s), 3.68(3H,     s), 3.8-4.4(2H, m), 5.1-6.0(3H, m), 6.5-7.3(3H, m)      43     ##STR147##      ##STR148##      43 0.7-1.0(6H, m),1.0-2.9(16H, m),3.68(3H, s), 3.6-3.9(4H, m), 5.3-6.1(3     H, m), 6.5-7.4(7H, m)      44     ##STR149##      ##STR150##      61 0.7-1.1(3H, m),1.1-2.9(24H, m),3.68(3H, s), 3.8-4.3(2H, m), 5.3-5.9(2     H, m), 6.5-7.0(2H, m)

EXAMPLE 45 Synthesis of2-methylthio-5-(6-carboxyhexylidene)-4-(3-hydroxyl-octenyl)-2-cyclopentenone##STR151##

To a solution of 345 mg of2-methylthio-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenoneobtained in Example 34 dissolved in 20 ml of acetone was added 220 ml of0.1M phosphate buffer of pH 8. While the mixture was stirred, 24 mg ofpig liver esterase was added thereto, and the mixture was stirred at30-35° C. for 150 hours. After the pH was adjusted to 4 with 0.1Nhydrochloric acid, ammonium sulfate was added to saturation and ethylacetate was added, followed by filtration. The filtrate was extractedwith ethyl acetate, and the organic layers were combined and washed withsaturated aqueous sodium chloride. The product was dried over anhydrousmagnesium sulfate, filtered and concentrated, followed by silica gelchromatography to give 193 mg (yield 58%) of2-methylthio-5-(6-carboxyhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone.

Spectrum data

¹ H-NMR CDCl₃ δ

0.86 (3H, brt, J=5.6 Hz), 1.1-2.5 (20H, m),

2.34 (3H, s), 3.9-4.2 (2H, m), 5.2-5.9

(2H, m), 6.6-6.8 (2H, m).

EXAMPLE 46 Synthesis of2-methylsulfinyl-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone##STR152##

A solution of 252.2 mg of2-methylthio-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenoneobtained in Example 34 in dichloromethane (20 ml) was cooled to 0° C.,and a solution of 3-chloroperbenzoic acid (129.8 mg) in dichloromethane(10 ml) was added dropwise thereto. After the mixture was stirred at 0°C. for 1 hour, ethyl acetate and saturated aqueous sodiumhydrogencarbonate was added, and the product was extracted into theorganic layer. The extract was successively washed with saturatedaqueous sodium chloride, saturated aqueous ammonium chloride andsaturated aqueous sodium chloride, then dried over anhydrous magnesiumsulfate, and filtered, followed by concentration. The concentrate wassubjected to silica gel chromatography to give 186.8 mg (yield 71%) of amixture of isomers of2-methylsulfinyl-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone.

Spectrum data

¹ H-NMR CDCl₃ δ

0.89 (3H, brt), 1.1-2.4 (19H, m), 2.86 and

2.88 (3H, s), 3.67 (3H, s), 4.0-4.3 (2H, m),

5.3-6.0 (2H, m), 6.72 (1H, t, J=7 Hz),

7.7-7.8 (1H, m).

EXAMPLE 47 Synthesis of2-methylsulfinyl-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone##STR153##

To a solution of 21.9 mg of2-methylthio-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenoneobtained in Example 34 in methanol (3 ml) was added a solution of sodiummetaperiodide (118.7 mg) in water (0.5 ml), and the mixture was stirredfor 18 hours. To the reaction mixture were added ethyl acetate andsaturated aqueous sodium chloride, and the product was extracted intothe organic layer. The extract was washed with saturated aqueous sodiumchloride, dried over anhydrous magnesium sulfate and filtered, followedby concentration. The concentrate was subjected to silica gelchromatography to give 9.6 mg (yield 42%) of2-methylsulfinyl-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone.

EXAMPLE 48 Synthesis of2-methylsulfinyl-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone##STR154##

To a solution of 17.6 mg of2-methylthio-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenoneobtained in Example 34 in methanol (0.5 ml) was added a solution of2KHSO₅ ·KHSO₄ ·K₂ SO₄ (27.4 mg) in water (0.2 ml) at 0° C., and themixture was stirred for 30 minutes. To the reaction mixture were addedethyl acetate and saturated aqueous sodium hydrogencarbonate, and theproduct was extracted into the organic layer. The extract was washedwith saturated aqueous sodium chloride, dried over anhydrous magnesiumsulfate and filtered, followed by concentration. The concentrate wassubjected to silica gel chromatography to obtain 3 mg (yield 16%) of2-methylsulfinyl-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone.

EXAMPLE 49 Synthesis of2-methylsulfonyl-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone##STR155##

A solution of 18 mg of2-methylthio-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenoneobtained in Example 34 in dichloromethane (1.5 ml) was cooled to 0° C.,and a solution of 3-chloroperbenzoic acid (15.7 mg) in dichloromethane(1 ml) was added dropwise thereto. After the mixture was stirred at 0°C. for 2 hours, ethyl acetate and saturated aqueous sodiumhydrogencarbonate were added and the product was extracted into theorganic layer. The extract was successively washed with saturatedaqueous sodium chloride, saturated aqueous ammonium chloride andsaturated aqueous sodium chloride, then dried over anhydrous magnesiumsulfate and filtered, followed by concentration. The concentrate wassubjected to silica gel chromatography to give 16.6 mg (yield 85%) of2-methylsulfonyl-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone.

Spectrum data

¹ H-NMR CDCl₃ δ

0.7-1.0 (m 3H), 1.1-2.4 (m, 18H), 3.16

(s, 3H), 3.66 (s, 3H), 4.0-4.5 (m, 2H),

5.3-6.0 (m, 2H), 6.82 (t, J=7 Hz, 1H), 8.06

(d, J=3 Hz, 1H).

EXAMPLE 50 Synthesis of5-(6-methoxycarbonylhexylidene)-2-methylsulfinyl-4-(1-octenyl)-2-cyclopentenone##STR156##

A solution of 9 mg of5-(6-methoxycarbonylhexylidene-2-methylthio-4-(1-octenyl)-2-cyclopentenoneobtained in Example 19 dissolved in 2 ml of methanol, and 500 μl of anaqueous solution of 150 mg of sodium periodate was added, and themixture was stirred for 5 hours. Saturated aqueous sodium chloride wasadded, and the mixture was extracted with ethyl acetate. The organiclayer was washed with saturated aqueous sodium chloride and dried overanhydrous magnesium sulfate. After filtration and concentration, theconcentrate was subjected to silica gel column chromatography to give4.3 mg (yield 48%) of a mixture of isomers of5-(6-methoxycarbonylhexylidene)-2-methylsulfinyl-4-(1-octenyl)-2-cyclopentenone.

Spectrum data

¹ H-NMR (CDCl₃) δ

0.88 (3H, brt, J=6.0 Hz), 1.0-2.5 (20H, m),

2.86 and 2.88 (3H, s), 3.67 (3H, s), 3.9-4.3

(1H, m), 5.0-6.0 (2H, m), 6.6-6.9 (1H, m),

7.80 (1H, d, J=3 Hz)

EXAMPLE 51 Syntheses of2,3-epoxy-4-trimethylsilyloxy-4-(4-phenoxybutyl)cyclopentanone and2,3-epoxy-4-hydroxy-4-(4-phenoxybutyl)cyclopentanone ##STR157##

To a solution of 2.49 g of4-trimethylsilyloxy-4-(4-phenoxybutyl)-2-cyclopentenone dissolved in 50ml of methanol was added 3.9 ml of an aqueous 30% hydrogen peroxideunder ice-cooling and stirring. An amount of 390 μl of 1N aqueous sodiumhydroxide was added, and the mixture was stirred for 2 hours. Thensaturated aqueous ammonium chloride was added, and the mixture wasextracted with ethyl acetate. The organic layer was washed withsaturated aqueous sodium chloride and dried over anhydrous magnesiumsulfate. After filtration and concentration, the concentrate wassubjected to silica gel column chromatography to give 892 mg (yield 34%)of 2,3-epoxy-4-trimethylsilyloxy-4-(4-phenoxybutyl)cyclopentanone and1.38 g (yield 53%) of2,3-epoxy-4-hydroxy-4-(4-phenoxybutyl)cyclopentanone.

Spectrum data

(C) ¹ H-NMR (CDCl₃) δ

0.20 (9H, s), 1.4-2.1 (6H, m), 2.16 (1H, d,

J=17.5 Hz), 2.57 (1H, d, J=17.5 Hz), 3.45

(1H, d, J=2.5 Hz), 3.77 (1H, d, J=2.5 Hz),

3.8-4.1 (2H, m), 6.8-7.1 (3H, m), 7.15-7.45

(2H, m).

(D) ¹ H-NMR (CDCl₃) δ

1.4-2.1 (6H, m), 2.31 (1H, d, J=16.3 Hz),

2.4 (1H, d, 16.3 Hz), 2.4-2.8 (1H, m),

3.35-3.6 (1H, m), 3.65-4.2 (3H, m), 6.7-7.05

(3H, m), 7.1-7.45 (2H, m).

EXAMPLE 52 Synthesis of2-methylthio-4-hydroxy-4-(4-phenoxybutyl)-2-cyclopentenone ##STR158##

To a solution of 25 mg of sodium thiomethoxide dissolved in methanol, 51μl of acetic acid was added, and the mixture was stirred for 10 minutes.Triethylamine (170 μl ) was then added, and after the mixture wasstirred for 10 minutes, a solution of 16 mg of2,3-epoxy-4-trimethylsilyloxy-4-(4-phenoxybutyl)cyclopentanone obtainedin Example 51 in 3 ml of methanol was added and the mixture was stirredfor 5 hours. Then saturated aqueous ammonium chloride was added, and themixture was extracted with ethyl acetate. The organic layer was washedwith saturated aqueous sodium chloride and dried over anhydrous sodiumsulfate. After filtration and concentration, the concentrate wassubjected to silica gel column chromatography to obtain 7.1 mg (yield51%) of 2-methylthio-4-hydroxy-4-(4-phenoxybutyl)-2-cyclopentenone.

Spectrum data

¹ H-NMR (CDCl₃) δ

1.4-2.0 (6H, m), 2.18 (1H, s), 2.34 (3H, s),

2.63 (1H, d, J=17.5 Hz), 2.72 (1H, d,

J=17.5 Hz), 4.0 (2H, brt, J=6.0 Hz), 6.76

(1H, s), 6.8-7.1 (3H, m), 7.15-7.45 (2H, m).

EXAMPLE 53 Synthesis of2-methylthio-4-hydroxy-4-(4-phenoxybutyl)-2-cyclopentenone ##STR159##

To a solution of 1.5 g of sodium thiomethoxide dissolved in 80 ml ofmethanol was added 1.8 ml of acetic acid under ice-cooling and stirring.After the mixture was stirred for 5 minutes, 4.8 ml of triethylamine wasadded, and the solution of 1.38 g of2,3-epoxy-4-hydroxy-4-(4-phenoxybutyl)cyclopentanone obtained in Example51 dissolved in 20 ml of methanol was added. After the mixture wasstirred for 4 hours, water was added and the mixture was extracted withethyl acetate. The organic layers were combined, washed with saturatedaqueous sodium chloride and dried over anhydrous magnesium sulfate.After filtration and concentration, the concentrate was subjected tosilica gel column chromatography to give 1.39 g (yield 83%) of2-methylthio-4-hydroxy-4-(4-phenoxybutyl)-2-cyclopentenone.

EXAMPLE 54 Synthesis of2-methylthio-4-(4-phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenone##STR160##

To a solution of 400 mg of2-methylthio-4-hydroxy-4-(4-phenoxybutyl)-2-cyclopentenone obtained inExample 52 or Example 53 dissolved in 4 ml of dimethylformamide wereadded 279 mg of imidazole and 260 μl of chlorotrimethylsilane, underice-cooling and stirring, and the mixture was stirred at 0° C. for 3hours. The reaction mixture was extracted with an addition of water andhexane. The organic layer was washed with saturated aqueous sodiumchloride, and the product dried over anhydrous sodium sulfate, filteredand concentrated, followed by silica gel column chromatography, to give445 mg (yield 89%) of2-methylthio-4-(4-phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenone.

Spectrum data

¹ H-NMR (CDCl₃) δ

0.11 (9H, s), 1.3-1.9 (6H, m), 2.35 (3H, s),

2.66 (2H, s), 3.95 (2H, t, J=5.9 Hz), 6.80

(1H, s), 6.8-7.45 (5H, m).

EXAMPLE 55 Synthesis of2-methylthio-4-octyl-4-trimethylsilyloxy-2-cyclopentenone ##STR161##

To a solution of 3.3 g of 4-octyl-4-trimethylsilyloxy-2-cyclopentenonedissolved in 50 ml of methanol was added, under ice-cooling andstirring, 5.0 ml of an aqueous 30% hydrogen peroxide, and 500 μl of anaqueous 1N sodium hydroxide was added. After the mixture was stirred for3.5 hours, saturated aqueous ammonium chloride was added, and themixture was extracted with ethyl acetate The organic layer was washedwith saturated aqueous sodium chloride and dried over anhydrousmagnesium sulfate. The product was filtered and concentrated to give acrude oil of 2,3-epoxy-4-octyl-4-trimethylsilyloxycyclopentanone.

A solution of 910 mg of sodium thiomethoxide dissolved in 100 ml ofmethanol was stirred under ice-cooling and stirring for 15 minutes.Triethylamine (6 ml) was added, and after the mixture was stirred for 10minutes, a solution of the above crude oil of2,3-epoxy-4-octyl-4-trimethylsilyloxycyclopentanone in 15 ml of methanolwas added dropwise. After the mixture was stirred for 6 hours, thereaction mixture was poured onto saturated aqueous ammonium chloride,and the mixture was extracted with ethyl acetate. The organic layer waswashed with saturated aqueous sodium chloride, dried over anhydroussodium sulfate, filtered and concentrated to give a crude oil of2-methylthio-4-hydroxy-4-octyl-2-cyclopentenone.

To a solution of the crude oil dissolved in 80 ml of dimethylformamidewas added 2.2 g of imidazole, under ice-cooling and stirring, and then2.0 g of chlorotrimethylsilane was added, followed by stirring at 0° C.for 4.5 hours. The mixture was extracted with addition of water andhexane, and the organic layer was washed with saturated aqueous sodiumchloride. After drying over anhydrous sodium sulfate, filtration andconcentration, the concentrate was subjected to silica gel columnchromatography to give 1.41 g (yield 37%) of2-methylthio-4-octyl-4-trimethylsilyloxy-2-cyclopentenone.

Spectrum data

¹ H-NMR CDCl₃ δ

0.06 (9H, s), 0.89 (3H, brt), 1.1-1.9

(14H, m), 2.34 (3H, s), 2.64 (2H, s), 6.85

(1H, s).

EXAMPLES 56-60

2-Substituted-2-cyclopentenones listed in Table 6 were obtained in thesame manner a in Example 55.

                                      TABLE 6                                     __________________________________________________________________________    Exam-                                                                         ple                      2-Substituted-2-        Yield                                                                             NMR                      No. Starting compound    cyclopentanones         (%) (δCDCl.sub.3)      __________________________________________________________________________    56                                                                                 ##STR162##                                                                                         ##STR163##             41  0.09(9H, s), 1.4-1.9                                                          4H, m), 2.3-2.9 (4H,                                                          m), 2.35 (3H, s),                                                             3.82 (6H, s),                                                                 6.6-7.1 (4H, m)          57                                                                                 ##STR164##                                                                                         ##STR165##             37  0.08(9H, s), 0.83                                                             (9H, d, J=4.4 Hz),                                                            0.9-2.1(12H, m),                                                              2.34(3H, s), 2.65                                                             (2H, s), 6.87(1H,                                                             s)                       58                                                                                 ##STR166##                                                                                         ##STR167##             33  0.05(9H, s), 0.7-1.1                                                          3H, m), 1.1-2.0 (6H,                                                          m), 2.34 (3H, s),                                                             2.66 (2H, s), 6.83                                                            (1H, s)                  59                                                                                 ##STR168##                                                                                         ##STR169##             26  0.01-0.08(15H, m),                                                            0.89(9H, s), 1.0-2.0                                                          11H, m), 2.36 (3H,                                                            s), 2.68 (2H, s),                                                             4.6-4.85 (1H, m),                                                             5.4-5.8 (2H, m),                                                              6.85(1H, s)              60                                                                                 ##STR170##                                                                                         ##STR171##             56  0.07(9H, s), 0.85                                                             (3H, s), 2.35 (3H,                                                            s), 2.68 (2H, s),                                                             6.84(1H,                 __________________________________________________________________________                                                         s)                   

EXAMPLE 61 Synthesis of2-phenylthio-4-trimethylsilyloxy-4-(4-phenoxylbutyl) -2-cyclopentenone##STR172##

A 1.8 g amount of 2,3-epoxy-4-hydroxy-4-(4-phenoxybutyl)cyclopentanoneobtained in Example 51 was dissolved in 15 ml of methanol, followed byadding 1.0 ml of triethylamine. Then, 790 mg of thiophenol was added,followed by stirring for 1.5 hours. The reaction mixture was poured onan aqueous saturated potassium hydrogensulfate solution, followed byextracting with ethyl acetate. The organic layer was washed with asaturated aqueous sodium chloride solution, followed by drying onanhydrous magnesium sulfate. After filtering and concentrating, theresultant crude oily product of2-phenylthio-4-hydroxy-4-(4-phenoxybutyl)-2-cyclopentenone was dissolvedin 20 ml of dimethylformamide and, while water cooling with stirring 1.5g of imidazole was added. Thereafter, 1.4 g of chlorotrimethyl silanewas added. The mixture was stirred at 0° C. for 5 hours, water andhexane was added to extract. The organic layer was washed with asaturated aqueous sodium chloride solution, dried over anhydrous sodiumsulfate, and, after filtering and concentrating, the concentrate wassubjected to silica gel column chromatography. Thus, 0.89 g (yield 37%)of 2-phenylthio-4-timethylsilyloxy-4-(4-phenoxylbutyl)-2-cyclopentenonewas obtained.

Spectrum data

¹ H-NMR CDCl₃ δ

0.05 (9H, S), 1.1-1.9 (6H, m), 2.63 (2H, S), 3.95 (2H, t, J=6.0 Hz),6.8-7.7 (11H, m)

EXAMPLE 62 Synthesis of5-[4,7-bis(t-butyldimethylsilyloxy)-1-hydroxy-2-heptenyl]-2-methylthio-4-(4-phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenone##STR173##

An amount of 1.195 g of2-methylthio-4-(phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenoneobtained in Example 54 was taken up, and after nitrogen replacement, 7.0ml of dry ether and 7.0 ml of dry hexane was added. After 857 μl ofdiisopropylethylamine was added, the mixture was cooled to -70° C. A1.0M dibutylborontrifrate dichloromethane solution (4.57 ml) was added,and the mixture was stirred at -70° C. for 1 hour. A solution of 1.47 gof 4,7-bis(t-butyldimethylsilyloxy)-2-heptenal in 10 ml of dry ether wascooled and added, followed by stirring at -70° C. for 3 hours. Saturatedaqueous ammonium chloride was added, and the mixture was extracted withether. The organic layers were combined, washed with saturated aqueoussodium chloride and dried over anhydrous magnesium sulfate. Afterfiltration and concentration, the concentrate was subjected to silicagel column chromatography to give 1.81 g (yield 75%) of a mixture ofisomers of5-[4,7-bis(t-butyldimethylsilyloxy)-1-hydroxy-2-heptenyl]-2-methylthio-4-(4-phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenone.

Spectrum data

Less polar isomer

¹ H-NMR CDCl₃ δ

0-0.2 (m, 21H), 0.90 (s, 18H), 1.0-2.1

(m, 10H), 2.34 (s, 3H), 2.74 (d, 1H, J=7.0 Hz),

3.5-3.7 (m, 2H), 3.98 (t, 2H, J=5.4 Hz),

4.05-4.35 (m, 1H), 4.35-4.7

(m, 1H), 5.5-6.2 (m, 2H), 6.7-7.1 (m, 4H), 7.1-7.5 (m, 2H).

More polar isomer

¹ H-NMR CDCl₃ δ

0-0.2 (m, 21H), 0.90 (s, 18H), 1.1-2.1

(m, 10H), 2.34 (s, 3H), 2.77 (d, 1H, J=6.3 Hz),

3.45-3.7 (m, 2H), 3.97 (t, 2H, J=5.3 Hz),

4.05-4.3 (m, 1H), 4.4-4.8 (m, 1H),

5.5-6.2 (m, 2H), 6.7-7.1 (m, 4H), 7.1-7.5

(m, 2H).

EXAMPLES 63-71

2-Substituted-2-cyclopentenones listed in Table 7 were obtained in thesame manner as in Example 62.

                                      TABLE 7                                     __________________________________________________________________________    Ex-                                                                           am-                                                                           ple                                                                              Starting compound                                Yield                                                                             NMR                   No.                                                                              2-Substituted-2-cyclopentenones                                                                 Aldehydes    2-Substituted-2-cyclopentenones                                                                 (%) (δ                                                                      CDCl.sub.3)           __________________________________________________________________________    63                                                                                ##STR174##                                                                                      ##STR175##                                                                                 ##STR176##       65  0.07(9H, s),                                                                  1.1-2.8(22H, m),                                                              2.35(3H, s),                                                                  3.67(3H, s),                                                                  3.8-4.3 (3H, m),                                                              6.7-7.5 (6H, m)       64                                                                                                  ##STR177##                                                                                 ##STR178##       47  0.06(9H, s),                                                                  1.1-2.9(14H, m),                                                              2.35(3H, s),                                                                  3.75(3H, s),                                                                  3.7-4.3 (3H, m),                                                              6.6-7.5 (10H, m)      65                                                                                ##STR179##                                                                                      ##STR180##                                                                                 ##STR181##       55  0.07(9H, s),                                                                  0.7-1.0(3H, brt),                                                             1.0-2.0 (18H, m),                                                             .5-2.9(2H, m),                                                                3.7-4.0 (1H, m),                                                              4.0 (2H, brt,                                                                 J=6.0Hz), 6.7-7.5                                                             11H, m)               66                                                                                ##STR182##                                                                                      ##STR183##                                                                                 ##STR184##       37  0.17(9H, s),                                                                  1.0-2.1(12H, m),                                                              2.1-2.8 (6H, m),                                                              2.35 (3H, s),                                                                 3.65 (3H, s),                                                                 3.7-4.3(1H, m),                                                               3.86(6H, s),                                                                  6.6-7.1 (4H, m)       67                                                                                ##STR185##                                                                                      ##STR186##                                                                                 ##STR187##       48  0.08(9H, s),                                                                  0.83(9H, d,                                                                   J=4.5Hz),                                                                     0.9-2.9(24H, m),                                                              2.35(3H, s),                                                                  3.68(3H, s),                                                                  3.71-4.1 (1H, m),                                                             6.86 (1H, s)          68                                                                                ##STR188##                                                                                      ##STR189##                                                                                 ##STR190##       42  0.05(9H, s),                                                                  0.7-1.0(3H, brt),                                                             1.0-2.9 (18H, m),                                                             .36(3H, s),                                                                   3.69(3H, s),                                                                  3.7-4.0(1H, m),                                                               6.87 (1H, s)          69                                                                                ##STR191##                                                                                      ##STR192##                                                                                 ##STR193##       38  0.01-0.09 (15H,                                                               m), 0.89(9H, s),                                                              1.0-2.9(19H, m),                                                              2.36(3H, s), 3.68                                                             (3H, s), 3.8-4.0                                                              (1H,                                                                          m), 4.6-4.8(1H,                                                               m), 5.3-5.9 (2H,                                                              m), 6.89 (1H, s)      70                                                                                ##STR194##                                                                                      ##STR195##                                                                                 ##STR196##       51  0.06(9H, s),                                                                  1.25(3H, s),                                                                  1.1-2.8(12H, m),                                                              2.36(3H, s),                                                                  3.68(3H, s),                                                                  3.7-4.0 (1H, m),                                                              6.87 (1H, s)          71                                                                                ##STR197##                                                                                      ##STR198##                                                                                 ##STR199##       76  0.19(9H, s),                                                                  0.7-1.0(3H, brt),                                                             1.0-2.2 (23H, m),                                                             .31(2H, t, J=7.2                                                              Hz), 2.35(3H, s),                                                             .45(1H, d),                                                                   3.67(3H, s),                                                                  3.8-4.1(1H, m),                                                               6.75(1H, (1H,         __________________________________________________________________________                                                            s)                

EXAMPLE 72 Synthesis of5-(1,4,7-trihydroxy-2-heptenyl)-4-hydroxy-2-methylthio-4-(4-phenoxybutyl)-2-cyclopentenone##STR200##

To a solution of 270 mg of5-[4,7-bis(t-butyldimethylsilyloxy)-1-hydroxy-2-heptenyl]-2-methylthio-4-(4-phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenoneobtained in Example 62 dissolved in 15 ml of acetonitrile, 2 ml ofpyridine was added. While stirring the mixture under ice-cooling, 1 mlof a hydrogen fluoride-pyridine solution was added and the mixture wasstirred at 0° C.-room temperature for 16 hours. The mixture was pouredonto saturated aqueous sodium hydrogencarbonate, and the mixture wasextracted with ethyl acetate. The organic layers were combined, washedwith saturated aqueous sodium chloride and dried over anhydrousmagnesium sulfate. After filtration and concentration, the concentratewas subjected to silica gel chromatography to give 114 mg (yield 71%) of5-(1,4,7-trihydroxy-2-heptenyl)-4-hydroxy-2-methylthio-4-(4-phenoxybutyl)-2-cyclopentenone.

Spectrum data

¹ H-NMR CDCl₃ δ

1.1-2.2 (15H, m), 2.35 (3H, s), 2.6-2.9

(1H, m), 3.5-3.7 (2H, m), 3.97 (2H, t, J=5.3 Hz),

4.0-4.3 (1H, m), 4.4-4.8 (1H, m),

5.5-6.2 (2H, m), 6.7-7.1 (4H, m), 7.1-7.5

(2H, m).

EXAMPLE 73 Synthesis of2-methylthio-5-(1-hydroxy-6-methoxycarbonylhexyl)-4-hydroxy-4-octyl-2-cyclopentenone##STR201##

To a solution of 63 mg of2-methylthio-5-(1-hydroxy-6-methoxycarbonylhexyl)-4-octyl-4-trimethylsilyloxy-2-cyclopentenoneobtained in Example 71 dissolved in 6 ml of acetonitrile was added 130μl of pyridine. A hydrogen fluoride-pyridine solution (260 μl) wasadded, and the mixture was stirred for 18 hours. The reaction mixturewas poured onto saturated aqueous sodium hydrogencarbonate, and themixture was extracted with ethyl acetate. The organic layers werecombined, washed with saturated aqueous sodium chloride and dried overanhydrous magnesium sulfate. After filtration and concentration, theconcentrate was subjected to silica gel column chromatography to give 22mg (yield 41%) of2-methylthio-5-(1-hydroxy-6-methoxycarbonylhexyl)-4-hydroxy-4-octyl-2-cyclopentenone.

Spectrum data

¹ H-NMR CDCl₃ δ

0.86 (3H, t, J=5.7 Hz), 1.1-2.1 (24H, m),

2.2-2.5 (2H, m), 2.35 (3H, s), 2.45 (1H, d),

3.67 (3H, s), 3.8-4.1 (1H, m), 6.75 (1H, s).

EXAMPLE 74 Synthesis of5-(1,4,7-trihydroxy-2-heptenyl)-4-hydroxy-2-methylsulfinyl-4-(4-phenoxybutyl)-2-cyclopentenone ##STR202##

To a solution of 35 mg of5-(1,4,7-trihydroxy-2-heptenyl)-4-hydroxy-2-methylthio-4-(4-phenoxybutyl)-2-cyclopentenoneobtained in Example 72 dissolved in 2 ml of dichloromethane was added 16mg of 3-chloroperbenzoic acid, and the mixture was stirred for 3 hours.Saturated aqueous sodium hydrogencarbonate was added, and the mixturewas extracted with ethyl acetate. The organic layers were combined,washed with saturated aqueous sodium chloride, dried over anhydrousmagnesium sulfate, filtered and concentrated, followed by silica gelcolumn chromatography to give 7.3 mg (yield 46%) of5-(1,4,7-trihydroxy-2-heptenyl)-4-hydroxy-2-methylsulfinyl-4-(4-phenoxybutyl)-2-cyclopentenone.

Spectrum data

¹ H-NMR CDCl₃ δ

1.2-2.3 (15H, m), 2.84 (3H, s), 2.6-3.0

(1H, m), 3.5-3.7 (2H, m), 3.95 (2H, t, J=5.7 Hz),

4.0-4.3 (1H, m), 4.4-4.8 (1H, m), 5.5-6.2 (2H, m), 6.7-7.1 (3H, m),7.1-7.5

(3H, m).

EXAMPLE 75 Synthesis of5-[4,7-bis(t-butyldimethylsilyloxy)-2-heptenylidene]-2-methylthio-4-(4-phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenone##STR203##

To a solution of 1.00 g of5-[4,7-bis(t-butyldimethylsilyloxy)-1-hydroxy-2-heptenyl]-2-methylthio-4-(4-phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenoneobtained in Example 62 dissolved in 10 ml of dichloromethane was addedunder ice-cooling and stirring 497 mg of dimethylaminopyridene, and then147 μl of methanesulfonyl chloride was added dropwise. The temperatureof the mixture was gradually elevated to room temperature, and thenstirred for 6 hours. Saturated aqueous potassium hydrogensulfate wasadded, and the mixture was extracted with ethyl acetate. The organiclayers were combined, washed with saturated aqueous sodiumhydrogencarbonate and with saturated aqueous sodium chloride in theorder mentioned, and dried over anhydrous sodium sulfate. Afterfiltration and concentration, the concentrate was subjected to silicagel chromatography to give 644 mg (yield 66%) of low polarity isomer and255 mg (yield 26%) of high polarity isomer of5-[4,7-bis(t-butyldimethylsilyloxy)-2-heptenylidene]-2-methylthio-4-(4-phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenone.

Spectrum data

Less polar isomer (F)

¹ H-NMR CDCl₃ δ

0-0.1 (m, 21H), 0.90 (s, 9H), 0.93 (s, 9H),

1.1-2.1 (m, 10H), 2.36 (s, 3H), 3.4-3.75

(m, 2H), 3.98 (t, 2H, J=6.3 Hz), 4.1-4.5

(m, 1H), 6.13 (dd, 1H, J=15.0, 6.0 Hz), 6.54

(d, 1H, J=12.5 Hz), 6.63 (s, 1H), 6.75-7.10

(m, 3H), 7.15-7.45 (m, 2H), 7.68 (dd, 1H, J=15.0,

12.5 (Hz).

More polar isomer (E)

¹ H-NMR CDCl₃ δ

0-0.1 (m, 21H), 0.89 (s, 18H), 1.1-2.2

(m, 10H), 2.37 (s, 3H), 3.4-3.75 (m, 2H), 3.93

(t, 2H, J=6.3 Hz), 4.15-4.55 (m, 1H),

5.9-6.5 (m, 1H), 6.67 (s, 1H), 6.5-7.1

(m, 5H), 7.15-7.45 (m, 2H).

EXAMPLES 76-84

2-Substituted-2-cyclopentenones listed in Table 8 were obtained in thesame manner as in Example 75.

    TABLE 8      Example No. Starting compound 2-Substituted-2-cyclopentenone Yield (%)     NMR (δCDCl.sub.3)            76      ##STR204##      ##STR205##      72 0.07(9H, s), 1.1-2.8(20H,m), 2.36(3H, s), 3.68(3H, s),3.9-4.3(2H,     m), 6.7-7.5(7H,m)  2-methylthio-5-[1-hydroxy-3-(4-methoxycarbonylcyclohex     yl)- 2-methylthio-5-[3-(4-methoxycarbonylcyclohexyl)propylidene]-     propyl]-4-(4-phenoxybutyl)-4-trimethylsilyloxy-2- 4-(4-phenoxybutyl)-4-tr     imethylsilyloxy-2-cyclopentenone  cyclopentenone      77     ##STR206##      ##STR207##      39 0.05(9H, s), 1.1-2.9(12H,m), 2.35(3H, s), 3.75(3H, s),3.8-4.2(2H,     m), 6.6-7.5(7H,m)  2-methylthio-5-[1-hydroxy-4-(4-methoxyphenyl)butyl]-4-     (4- 2-methylthio-5-[4-(4-methoxyphenyl)butylidene]-4-(4-phenoxy-     phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenone butyl)-4-trimethylsily     loxy-2-cyclopentenone      78     ##STR208##      ##STR209##      44 0.06(9H, s), 0.7-1.0(3H,brt), 1.0-2.2(18H, m), 4.0(2H, brt, J=5.8Hz),      6.7-7.5(12H, m)  2-phenylthio-5-(1-hydroxyoctyl)-4-(4-phenoxybutyl)-4-(4     - 2-phenylthio-5-octenylidene-4-(4-phenoxybutyl)-4-trimethyl-  phenoxybut     yl)-4-trimethylsiloxy-2-cyclopentenone silyloxy-2-cyclopentenone  79      ##STR210##      ##STR211##      71 0.09(9H, s), 1.0-2.0(10H,m), 2.0-2.8(5H, m), 2.35(3H, s), 3.63(3H,     s), 3.84(6H, s), 4.8-5.2(1H, m),6.7-7.1(4H, m)  2-methylthio-5-(1-hydroxy     -6-methoxycarbonylhexyl)-4-[3-(3,4- 2-methylthio-5-(6-methoxy-carbonylhex     ylidene)-4-[3-(3,4-  dimethoxyphenyl)propyl]-4-trimethylsilyloxy-2-cyclop     entenone dimethoxyphenyl)propyl]-4-trimethylsilyloxy-2-cyclopentenone     80      ##STR212##      ##STR213##      54 0.09(9H, s), 0.83(9H, d,J=4.5Hz), 0.9-2.5(22H, m),2.35(3H, s),     3.67(3H, s),6.6-7.0(2H, m)  2-methylthio-5-(1-hydroxy-6-methoxycarbonylhe     xyl)-4-(3,7- 2-methylthio-5-(6-methoxy-carbonylhexylidene)-4-(3,7-     dimethyloctyl)-4-trimethylsilyloxy-2-cyclopentenone dimethloctyl)-4-trime     thylsilyloxy-2-cyclopentenone      81     ##STR214##      ##STR215##      62 0.06(9H, s), 0.7-1.0(3H,brt), 1.0-2.4(16H, m), 2.35(3H, s), 3.68(3H,     s), 6.6-7.0(2H, m)  2-methylthio-5-(1-hydroxy-6-methoxycarbonylhexyl)-4-(     1- 2-methylthio-5-(6-methoxy-carbonylhexylidene)-4-(1-  hexynyl)-4-trimet     hylsilyloxy-2-cyclopentenone hexynyl)-4-trimethylsilyloxy-2-cyclopentenon     e      82     ##STR216##      ##STR217##      49 0.01-0.10(15H, m), 0.89(9H,s), 1.0-2.4(17H, m), 2.36(3H, s),     3.67(3H, s), 4.6-4.8(1H, m), 5.3-5.9(2H, m),6.6-7.1(2H, m)  2-methylthio-     5-(1-hydroxy-6-methoxycarbonyl-2-hexynyl)-4-(3- 2-methylthio-5-(6-methoxy     carbonyl-2-hexynylidene)-4-(3-t-  t-butyldimethylsilyloxy-3-cyclohexyl-1-     propenyl)-4-trimethyl- butyldimethylsilyloxy-3-cyclohexyl-1-propenyl)-4-t     rimethyl-  silyloxy-2-cyclopentenone silyloxy-2-cyclopentenone  83      ##STR218##      ##STR219##      51 0.07(9H, s), 1.29(3H, s),1.1-2.4(10H, m), 2.36(3H,s), 3.69(3H, s),     6.6-7.1(2H,m)  2-methylthio-5-(1-hydroxy-6-methoxycarbonylhexyl)-4-     2-methylthio-5-(6-methoxycarbonylhexylidene)-4-methyl-4-tri-  methyl-4-tr     imethylsilyloxy-2-cyclopentenone methylsilyloxy-2-cyclopentenone  84      ##STR220##      ##STR221##      40 0.03(9H, s), 0.7-1.0(3H,brt), 1.0-2.0(20H, m),2.1-2.5(4H, m),     2.34(3H, s),3.68(3H, s), 6.5-6.9(2H, m)  2-methylthio-5-(1-hydroxy-6-meth     oxycarbonylhexyl)-4- 2-methylthio-5-(6-methoxycarbonylhexylidene)-4-octyl     -4-tri-  octyl-4-trimethylsilyloxy-2-cyclopentenone methylsilyloxy-2-cycl     opentenone

EXAMPLE 85 Syntheses of5-](Z)-4,7-dihydroxy-2-heptenylidene]-2-methylthio-4-4-trimethylsilyloxy-(4-phenoxybutylidene)-2-cyclopentenoneand5-[(Z)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxybutyl)-2-cyclopentenone##STR222##

To a solution of 9 ml of pyridine dissolved in 50 ml of acetonitrile wasadded, 4.5 ml of hydrogen fluoride-pyridine solution, under ice-coolingand stirring. A solution of 1.41 g of5-[(Z)-4,7-bis(t-butyldimethylsilyloxy)-2-heptenylidene]-2-methylthio-4-(4-phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenoneobtained in Example 75 in 15 ml of acetonitrile was added, and themixture was stirred at 0° C. for 10 minutes, and at room temperature for8 hours. The reaction mixture was poured onto saturated aqueous sodiumhydrogencarbonate, and the mixture was extracted for 3 times with ethylacetate. The organic layers were combined, washed once with saturatedaqueous sodium hydrogencarbonate and twice with saturated aqueous sodiumchloride. The product was dried over anhydrous magnesium sulfate,filtered and concentrated. The oily product obtained was subject tosilica gel column chromatography to obtain 158 mg (yield 20%) of5-[(Z)-4,7-dihydroxy-2-heptenylidene]-2-methylthio-4-(4-phenoxybutylidene)-2-cyclopentenoneand 353 mg (yield 43%) of5-[(Z)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxybutyl)-2-cyclopentenone.

Spectrum data

(G) ¹ H-NMR-CDCl₃ δ

1.4-2.9 (m, 10H), 2.26 (s, 3H), 3.4-3.9

(m, 2H), 4.01 (t, 2H, J=6.0 Hz), 5.83 (t,

1H, J=7.9 Hz), 6.23 (dd, 1H, J=16.0,

6.5 Hz), 6.74 (d, 1H, J=11.0 Hz), 6.7-7.5

(m, 8H), 7.87 (dd, J=16.0, 11.0 Hz).

(H) ¹ H-NMR-CDCl₃ δ

1.2-2.7(13H, m), 2.33 (3H, s), 3.5-3.8

(2H, m), 3.94 (2H, t, J=6.0 Hz), 4.15-4.50

(1H, m), 6.15 (1H, dd, J=15.2, 6.4 Hz), 6.61

(1H, d, J=11.4 Hz), 6.62 (1H, s), 6.7-7.0

(3H, m), 7.1-7.4 (2H, m), 7.67 (1H, dd, J=15.4, 11.4 Hz).

EXAMPLE 86 Synthesis of5-[(Z)-4,7-dihydroxy-2-heptenylidene]-2-methylthio-4-(4-phenoxybutylidene)-2-cyclopentenone##STR223##

To 1.14 g of5-[(Z)-4,7-bis(t-butydimethylsilyloxy)-2-heptenylidene]-2-methylthio-4-(4-phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenoneobtained in Example 75 was added 40 ml of a mixture of aceticacid:tetrahydrofuran:water=3:1:1, and the mixture was stirred at roomtemperature for 18 hours. After the mixture was concentrated with anaddition of toluene, saturated aqueous sodium hydrogen carbonate wasadded, and the mixture was extracted for 3 times with ethyl acetate. Theorganic layers were combined, washed successively with saturated aqueoussodium hydrogencarbonate and saturated aqueous sodium chloride, anddried over anhydrous magnesium sulfate. After filtration andconcentration, the concentrate was subjected to silica gel columnchromatography to give 407 mg (yield 61%) of5-[(Z)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxybutylidene)-2-cyclopentenone.

EXAMPLE 87 Synthesis of5-[(Z)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylsulfinyl-4-(4-phenoxybutylidene)-2-cyclopentenone##STR224##

To a solution of 20 mg of5-[(Z)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxybutylidene)-2-cyclopentenoneobtained in Example 85 or Example 86 dissolved in 3 ml of methanol wasadded a solution of 102 mg of sodium periodate in 500 μl of water, andthe mixture was stirred for 5 hours. Saturated aqueous sodium chloridewas added, and the mixture was extracted for 3 times with ethyl acetate.The organic layers were combined, and washed with saturated aqueoussodium chloride, followed by drying over anhydrous magnesium sulfate.After filtration and concentration, the concentrate was subjected tosilica gel column chromatography to give 13.3 mg (yield 64%) of5-[(Z)--4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylsulfinyl-4-(4-phenoxybutylidene)-2-cyclopentenone.

Spectrum data

¹ H-NMR CDCl₃ δ

1.2-2.2 (m, 7H), 2.2-3.2 (m, 3H), 2.85

(s, 3H), 3.5-3.8 (m, 2H), 4.03 (t, 2H, J=6.3 Hz),

4.1-4.6 (m, 1H), 6.0-6.75 (m, 2H),

6.75-7.15 (m, 5H), 7.15-7.45 (m, 3H) 7.81 (dd,

1H, J=15.0, 11.3 Hz), 8.29 and 8.36 (s, 1H).

EXAMPLE 88 Syntheses of5-[(Z)-4,7-dihydroxy-2-heptenyidene]-2-methylsulfinyl-4-(4-phenoxybutylidene)-2-cyclopentenoneand5-[(Z)-4,7-dihydroxy-2-heptenylidene]-2-methylsulfonyl-4-(4-phenoxybutylidene)-2-cyclopentenone##STR225##

To a solution of 280 mg of5-[(Z)-4,7-dihydroxy-2-heptenylidene]-2-methylthio-4-(4-phenoxybutylidene)-2-cyclopentenoneobtained in Example 85 or Example 86 dissolved in 15 ml ofdichloromethane was added a solution of 200 mg of 3-chloroperbenzoicacid in 5 ml of dichloromethane. Saturated aqueous sodiumhydrogencarbonate was added, and the mixture was extracted with ethylacetate. The organic layers were combined, washed with saturated aqueoussodium chloride and dried over anhydrous sodium sulfate. Afterfiltration and concentration, the concentrate was subjected to silicagel column chromatography to give 36 mg (yield 13%) of5-[(Z)-4-,7-dihydroxy-2-heptenylidene]-2-methylsulfinyl-4-(4-phenoxybutylidene)-2-cyclopentenoneand 66 mg (yield 24%) of5-[(Z)-4,7-dihydroxy-2-heptenylidene]-2-methylsulfonyl-4-(4-phenoxybutylidene)-2-cyclopentenone.

Spectrum data

(I) ¹ H-NMR CDCl₃ δ

1.3-2.3 (8H, m), 2.5-2.9 (2H, m), 3.10 and

3.11 (3H, s), 3.5-3.85 (2H, m), 4.00 (2H, t, J=5.9 Hz),

4.15-4.55 (1H, m), 6.0-6.75

(2H, m), 6.75-7.05 (4H, m), 7.05-7.40 (2H, m),

7.80 (1H, J=11.3, 15.0 Hz), 8.43 and 8.51

(1H, s).

EXAMPLE 89 Synthesis of2-methylsulfonyl-5-[(Z)-4,7-dihydroxy-2-heptenylidene]-4-(4-phenoxybutylidene)-2-cyclopetenone##STR226##

To a solution of 20 mg of2-methylthio-5-[(Z)-4,7-dihydroxy-2-heptenyldidene]-4-(4-phenoxybutylidne)-2-cyclopentenoneobtained in Example 85 or Example 86 dissolved in 2 ml of methanol wasadded 2 ml of an aqueous solution of 60 mg of 2KHSO₅ ·KHSO₄ ·K₂ SO₄, andthe mixture was stirred for 20 hours. Saturated aqueous sodiumhydrogencarbonate was added, and the mixture was extracted with ethylacetate. The organic layers were combined, and washed with saturatedaqueous sodium chloride, dried over anhydrous magnesium sulfate,filtered and concentrated, followed by silica gel chromatography to give5.6 mg (yield 26%) of2-methylsulfonyl-5-[(Z)-4,7-dihydroxy-2-heptenylidene]-4-(4-phenoxybutylidene)-2-cyclopentenone.

EXAMPLE 90 Synthesis of2-methylsulfonyl-5-[(Z)-4,7-dihydroxy-2-heptenylidene]-4-(4-phenoxybutylidene)-2-cyclopentenone##STR227##

To a solution of 6.5 mg of2-methylsulfinyl-5-[(Z)-4,7-dihydroxy-2-heptenylidene]-4-(4-phenoxybutylidene)-2-cyclopentenoneobtained in Example 87 or Example 88 dissolved in 1.5 ml ofdichloromethane was added 3 mg of 3-chloroperbenzoic acid, and themixture was stirred for 4 hours. Saturated aqueous sodiumhydrogencarbonate was added, and the mixture was extracted with ethylacetate. The extract was washed with saturated aqueous sodium chloride,dried over anhydrous magnesium sulfate, filtered and concentrated,followed by silica gel chromatography to give 3.9 mg (yield 60%) of2-methylsulfonyl-5-[(Z)-4,7-dihydroxy-2-heptenylidene]-4-(4-phenoxbutylidene)-2-cyclopentenone.

EXAMPLE 91 Synthesis of5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxybutyl)-2-cyclopentenone##STR228##

To 255 mg of5-[(E)-4,7-bis(t-butyldimethylsilyloxy)-2-heptenylidene]-2-methylthio-4-(4-phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenoneobtained in Example 75 was added 20 ml of a mixture of aceticacid:tetrahydrofuran:water=3:1:1, and the mixture was stirred at roomtemperature for 26 hours. After concentration with an addition oftoluene, saturated aqueous sodium hydrogencarbonate was added, and themixture was extracted 3 times with ethyl acetate. The organic layerswere combined, washed successively with saturated aqueous sodiumhydrogencarbonate and saturated aqueous sodium chloride, and dried overanhydrous magnesium sulfate. After filtration and concentration, theconcentrate was subjected to silica gel column chromatography to give 94mg (yield 63%) of5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxybutyl)-2-cyclopentenone.

EXAMPLE 92 Synthesis of5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxybutyl1-2-cyclopetenone##STR229##

To a solution of 660 mg of5-[(E)-4,7-bis(t-butyldimethylsilyloxy)-2-heptenylidene]-2-methylthio-4-(4-phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenoneobtained in Example 75 dissolved in 50 ml of acetonitrile was added 4 mlof pyridine, under ice-cooling and stirring. A hydrogen-pyridinesolution (2 ml) was added, and the mixture was stirred at 0° C. for 24hours. The reaction mixture was poured onto saturated aqueous sodiumhydrogencarbonate, and the mixture was extracted 3 times with ethylacetate. The organic layers were combined, washed with saturated sodiumchloride and dried over anhydrous magnesium sulfate. After filtrationand concentration, the concentrate was subjected to silica gel columnchromatography to give 320 mg (yield 83%) of5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxybutyl)-2-cyclopentenone.

Spectrum data

¹ H-NHR CDCl₃ δ

1.2-2.9 (m, 13H), 2.37 (s, 3H), 3.5-3.8

(m, 2H), 3.95 (t, 2H, J=6.3 Hz), 4.15-4.5

(m, 1H), 6.0-6.5 (m, 1H), 6.67 (s, 1H),

6.7-7.15 (m, 4H), 7.15-7.5 (m, 3H).

EXAMPLES 93-101

2-Substituted-2-cyclopentenones listed in Table 9 were obtained in thesame manner as in Example 92.

    TABLE 9        2-Substituted-2- Yield NMR Example No. Starting compound cyclopentenon     e (%) δCDCl.sub.3            93      ##STR230##      ##STR231##      47 1.1-2.8(21H, m), 2.36(3H, s), 3.68(3H, s),3.9-4.3(2H, m), 6.6-7.5(7H,      m)  2-methylthio-5-[3-(4-methoxy- 2-methylthio-5-[3-(4-methoxy-     carbonylcyclohexyl)propyli- carbonylcyclohexyl)propyli-  dene]-4-(4-pheno     xybutyl)-4- dene]-4-(4-phenoxybutyl)-4-  trimethylsilyloxy-2-cyclo-     hydroxy-2-cyclopentenone  pentenone      94     ##STR232##      ##STR233##      64 1.1-2.9(13H, m), 2.36(3H, s), 3.75(3H, s),3.8-4.2(2H, m), 6.6-7.5(7H,      m)  2-methylthio-5-[4-(4-methoxy- 2-methylthio-5-[4-(4-methoxy-     phenyl)butylidene]-4-(4- phenyl)butylidene]-4-(4-  phenoxybutyl)-4-trimet     hyl- phenoxybutyl)-4-hydroxy-2-  silyloxy-2-cyclopentenone cyclopentenone      95     ##STR234##      ##STR235##      75 0.7-1.0(3H, brt),1.0-2.2(18H, m),2.4-2.7(1H, m), 4.0(2H, brt,     J=5.8Hz), 6.7-7.5(12H, m)  2-phenylthio-5-octenylidene-4- 2-phenylthio-5-     octenylidene-4-  (4-phenoxybutyl)-4-trimethyl- (4-phenoxybutyl)-4-hydroxy     -2-  silyloxy-2-cyclopentenone cyclopentenone      96     ##STR236##      ##STR237##      58 1.0-3.2(17H, m), 2.35(3H, s), 3.64(3H, s),3.83(6H, s), 6.0-7.0(5H,     m)  2-methylthio-5-(6-methoxy- 2-methylthio-5-(6-methoxy-  carbonylhexyli     dene)-4-[3- carbonylhexylidene)-4-[3-(3,4-  (3,4-dimethoxyphenyl)propyl]-      dimethoxyphenyl)propyl]-4-  4-trimethylsilyloxy-2-cyclo- hydroxy-2-cyclo     pentenone  pentenone      97     ##STR238##      ##STR239##      71 0.84(9H, d,J=4.5Hz), 0.9-2.7(23H, m), 2.36(3H, s),3.68(3H, s),     6.6-7.0(2H, m)  2-methylthio-5-(6-methoxy- 2-methylthio-5-(6-methoxy-     carbonylhexylidene)-4-(3,7- carbonylhexylidene)-4-(3,7-  dimethyloctyl)-4     -trimethyl- dimethyloctyl)-4-hydroxy-2-  silyloxy-2-cyclopentenone     cyclopentenone      98     ##STR240##      ##STR241##      67 0.7-1.0(3H, brt),1.0-2.4(16H, m), 2.35(3H, s), 2.6-2.9(1H, m),     3.68(3H, s),6.6-7.0(2H, m)  2-methylthio-5-(6-methoxy- 2-methylthio-5-(6-     methoxy-  carbonylhexylidene)-4-(1- carbonylhexylidene)-4-(1-  hexynyl)-4     -trimethylsilyloxy- hexynyl)-4-hydroxy-2-cyclo-  2-cyclopentenone     pentenone      99     ##STR242##      ##STR243##      47 1.0-2.4(17H, m), 2.36(3H, s), 2.5-2.8(2H, m), 3.68(3H, s),4.6-4.8(1H,      m), 5.3-5.9(2H, m), 6.6-7.1(2H, m)  2-methylthio-5-(6-methoxy- 2-methylt     hio-5-(6-methoxy-  carbonyl-2-hexynylidene)-4- carbonyl-2-hexynilidene)-4     -  (3-t-butyldimethylsiloxy-3- (3-hydroxy-3-cyclohexyl-1-  cyclohexyl-1-p     ropenyl)-4- propenyl)-4-hydroxy-2-cyclo-  trimethylsilyloxy-2-cyclopen-     pentenone  tenone      100     ##STR244##      ##STR245##      72 1.30(3H, s), 1.1-2.7(11H, m), 2.35(3H, s),3.68(3H, s), 6.6-7.1(2H,     m)  2-methylthio-5-(6-methoxy- 2-methylthio-5-(6-methoxy-  carbonylhexyli     dene)-4- carbonylhexylidene)-4-  methyl-4-trimethylsilyloxy-2- methyl-4-h     ydroxy-2-cyclo-  cyclopentenone pentenone      101     ##STR246##      ##STR247##      62 0.86(3H, t,J=5.7Hz), 1.1-2.1(21H, m), 2.2-2.5(2H, m), 2.36(3H,     s),2.5-3.0(2H, m), 3.68(3H, s), 6.5-6.9(2H, m)  2-methylthio-5-(6-methoxy     - 2-methylthio-5-(6-methoxy-  carbonylhexylidene)-4-octyl-4- carbonylhexy     lidene)-4-  trimethylsilyloxy-2-cyclo- octyl-4-hydroxy-2-cyclo-     pentenone pentenone

EXAMPLE 102 Synthesis of5-[(Z)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylsulfinyl-4-phenoxybutyl-2-cyclopentenone##STR248##

To a solution of 110 mg of5-[(Z)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxybutyl)-2-cyclopentenoneobtained in Example 85 dissolved in 15 ml of dichloromethane was added asolution of 75 mg of 3-chloroperbenzoic acid in 5 ml of dichloromethane,under ice-cooling and stirring, and the mixture was stirred at 0° C. toroom temperature for 4 hours. Saturated aqueous sodium hydrogencarbonatewas added, and the mixture was extracted for 3 times with ethyl acetate.The organic layer was washed with saturated aqueous sodium chloride anddried over anhydrous sodium sulfate. After filtration and concentration,the concentrate was subjected to silica gel column chromatography togive 33 mg (yield 30%) of low polarity isomer and 19 mg (yield 17%) ofhigh polarity isomer of5-[(Z)-4,7-dihydroxyheptenylidene]-4-hydroxy-2-methylsulfinyl-4-phenoxybutyl-2-cyclopentenone.

Spectrum data

Less polar isomer

¹ H-NMR CDCl₃ δ

1.2-2.4 (13H, m), 2.84 (3H, s), 3.5-3.8

(2H, m), 3.94 (2H, t, J=5.9 Hz), 4.1-4.5

(1H, m), 6.0-6.4 (1H, m), 6.55-7.0 (4H, m),

7.1-7.8 (3H, m), 7.70 (1H, s).

More polar isomer

¹ H-NMR CDCl₃ δ

1.2-2.5 (13H, m), 2.86 (3H, s), 3.5-3.8

(2H, m), 3.95 (2H, t, J=5.9 Hz), 4.1-4.5

(1H, m), 6.23 (1H, dd, J=15.8, 5.5 Hz), 6.70

(1H, d, J=11.4 Hz), 6.7-7.0 (3H, m), 7.1-7.4

(2H, m), 7.61 (1H, dd, J=14.5, 12.0 Hz),

7.71 (1H, s)

EXAMPLE 103 Synthesis of5-[(Z)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylsulfonyl-4-(4-phenoxybutyl)-2-cyclopetenone##STR249##

To a solution of 24 mg of5-[(Z)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxybutyl)-2-cyclopentenoneobtained in Example 85 dissolved in 2 ml of dichloromethane was added asolution of 24 mg of 3-chloroperbenzoic acid in 240 μl ofdichloromethane, and the mixture was stirred for 18 hours. Saturatedaqueous sodium hydrogencarbonate was added, and the mixture wasextracted with ethyl acetate. The organic layers were combined, washedwith saturated aqueous sodium chloride and dried over anhydrousmagnesium sulfate. After filtration and concentration, the concentratewas subjected to silica gel column chromatography to give 7.3 mg (yield30%) of5-[(Z)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylsulfonyl-4-(4-phenoxybutyl)-2-cyclopentenone.

Spectrum data

¹ H-NMR CDCl₃ δ

1.0-2.5 (13H, m), 2.14 (1H, s), 3.6-3.8

(2H, m), 3.94 (2H, t, J=5.9 Hz), 4.1-4.5

(1H, m), 6.0-6.5 (1H, m), 6.5-7.0 (4H, m),

7.1-7.4 (2H, m), 7.4-7.8 (1H, m), 7.94 (1H,s).

EXAMPLE 104 Synthesis of5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylsulfinyl-4-(4-phenoxybutyl)-2-cyclopetenone##STR250##

To a solution of 71 mg of5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxybutyl)-2-cyclopentenoneobtained in Example 91 dissolved in 2 ml of dichloromethane was added asolution of 45 mg of 3-chloroperbenzoic acid in 2 ml of dichloromethane,and the mixture was stirred for 3 hours. Saturated aqueous sodiumhydrogencarbonate was added. The mixture was extracted twice with ethylacetate, and the organic layers were combined, washed with saturatedaqueous sodium chloride and dried over anhydrous sodium sulfate. Afterfiltration and concentration, the concentrate was subjected to silicagel column chromatography to give 27 mg (yield 38%) of low polarityisomer and 25 mg (yield 35%) of high polarity isomer of5-[(E)-4,7-dihydroxyheptenylidene]-4-hydroxy-2-methylsulfinyl-4-(4-phenoxybutyl)-2-cyclopentenone.

Spectrum data

Less polar isomer

¹ H-NMR CDCl₃ δ

1.1-2.7 (13H, m), 2.85 (3H, s), 3.5-3.8

(2H, m), 3.92 (2H, t, J=6.0 Hz), 4.1-4.4

(1H, m), 6.0-6.45 (1H, m), 6.65-7.05 (5H, m),

7.1-7.4 (2H, m), 7.71 (1H, s).

More polar isomer

¹ H-NMR CDCl₃ δ

1.1-2.3 (10H, m), 2.3-3.3 (3H, m), 2.87

(3H, s), 3.5-3.8 (2H, m), 3.91 (2H, t, J=6.0 Hz),

4.1-4.4 (1H, m), 6.0-6.5 (1H, m),

6.6-7.05 (5H, m), 7.1-7.5 (2H, m), 7.69

(1H, s).

EXAMPLE 105 Synthesis of5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylsulfonyl-4-(4-phenoxybutyl)-2-cyclopetenone##STR251##

To a solution of 165 mg of5-[(E)-4,7-dihydroxyheptenylidene]-4-hydroxy-2-methylsulfinyl-4-(4-phenoxybutyl)-2-cyclopentenoneobtained in Example 104 dissolved in 30 ml of dichloromethane was addeda solution 117 mg of 3-chloroperbenzoic acid in 5 ml of dichloromethane,and the mixture was stirred for 2 hours. The reaction mixture was pouredonto saturated aqueous sodium thiosulfate, and the mixture was extracted3 times with ethyl acetate. The organic layers were combined, washedtwice with saturated aqueous sodium hydrogencarbonate and with saturatedaqueous sodium chloride, and dried over anhydrous sodium sulfate. Afterfiltration and concentration, the concentrate was subjected tochromatography to give 78 mg (yield 47%) of5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylsulfonyl-4-(4-phenoxybutyl)-2cyclopentenone

Spectrum data

¹ H-NMR CDCl₃ δ

1.2-2.5 (13H, m), 3.15 (3H, s), 3.5-3.8

(2H, m), 3.93 (2H, t, J=5.9 Hz), 4.1-4.4

(1H, m), 6.1-6.4 (1H, m), 6.65-7.05 (4H, m),

7.05-7.4 (2H, m), 7.99 (1H, s).

EXAMPLE 106 Synthesis of5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylsulfinyl-4-(4-phenoxybutyl1-2-cyclopentenoneand5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylsulfonyl-4-(4-phenoxybutyl)-2-cyclopentenone##STR252##

To a solution of 10 mg of5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxybutyl)-2-cyclopentenoneobtained in Example 91 dissolved in 2 ml of dichloromethane was added4.8 mg of 3-chloroperbenzoic acid, and the mixture was stirred for 16hours. Saturated aqueous sodium hydrogencarbonate was added, the mixturewas extracted with ethyl acetate, and the organic layer was washed withsaturated aqueous sodium chloride. After drying over anhydrous sodiumsulfate, filtration and concentration, the concentrate was subjected tosilica gel chromatography to give 2.0 mg (yield 20%) of less polarisomer, 4.0 mg (yield 40%) of more polar isomer of5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylsulfinyl-4-(4-phenoxybutyl)-2-cyclopentenoneand 1.6 mg (yield 16%) of5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylsulfonyl-4-(4-phenoxybutyl)-2-cyclopentenone.

EXAMPLE 107 Synthesis of5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylsulfonyl-4-(4-phenoxybutyl)-2-cyclopetenone##STR253##

To a solution of 34 mg of5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxybutyl)-2-cyclopentenoneobtained in Example 91 dissolved in 2 ml of dichloromethane was added asolution 33 mg of 3-chloroperbenzoic acid in 330 μl of dichloromethane,and the mixture was stirred for 18 hours. Saturated aqueous sodiumhydrogencarbonate was added, and the mixture was extracted with ethylacetate. The organic layers were combined, washed with saturated aqueoussodium chloride and dried over anhydrous magnesium sulfate. Afterfiltration and concentration, the concentrate was subjected to silicagel column chromatography to give 13 mg (yield 38%) of5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylsulfonyl-4-(4-phenoxybutyl)-2-cyclopentenone.

EXAMPLE 108 Synthesis of2-methylsulfinyl-4-hydroxy-5-(6-methoxycarbonylhexylidene)-4-octyl-2-cyclopentenone##STR254##

To a solution of 12 mg of2-methylthio-4-hydroxy-5-(6-methoxycarbonylhexylidene)-4-octyl-2-cyclopentenoneobtained in Example 101 dissolved in 2 ml of dichloromethane was added6.5 mg of 3-chloroperbenzoic acid. After the mixture was stirred at 0°C. for 1 hour, saturated aqueous sodium hydrogencarbonate was added, andthe mixture was extracted with ethyl acetate. After washing withsaturated aqueous sodium chloride, the product was subjected to silicagel chromatography to obtain 7.3 mg (yield 61%).

Spectrum data

¹ H-NMR CDCl₃ δ

0.86 (3H, t, J=5.7 Hz), 1.1-2.1 (21H, m),

2.2-2.5 (2H, m), 2.5-3.0 (2H, m), 2.87

(3H, s), 3.68 (3H, s), 6.72 (1H, t, J=7 Hz),

7.70 (1H, s).

EXAMPLE 109 Synthesis of5-[(Z)-4,7-dihydroxy-2-heptenylidene]-2-methylthio-4-methoxy-4-(4-phenoxybutyl)-2-cyclopentenone##STR255##

To a solution of 2 mg of5-[(Z)-4,7-dihydroxy-2-heptenylidene]-2-methylthio-4-hydroxy-4-(4-phenoxybutyl)-2-cyclopentenoneobtained in Example 85 dissolved in 1 ml of methanol was added 0.5 μl ofacetic acid, and the mixture was stirred for 24 hours. Saturated aqueoussodium hydrogencarbonate was added, and the mixture was extracted withethyl acetate. The extract was dried over anhydrous magnesium sulfate,filtered and concentrated, followed by silica gel chromatography to give1.9 mg (yield 95%) of5-[(Z)-4,7-dihydroxy-2-heptenylidene]-2-methylthio-4-methoxy-4-(4-phenoxybutyl)-2-cyclopentenone.

Spectrum data

¹ H-NMR CDCl₃ δ

1.1-2.1 (12H, m), 2.36 (3H, s), 3.05 (3H, s),

3.55-3.8 (2H, m), 3.93 (2H, t, J=6.0 Hz),

4.1-4.5 (1H, m), 6.17 (1H, dd, J=6.2 ,

15.0 Hz), 6.46 (1H, d, J=11.0 Hz), 6.53

(1H, s), 6.7-7.0 (3H, m), 7.1-7.4 (2H, m),

7.72 (1H, dd, J=11.2, 15.3 Hz).

EXAMPLE 110 Synthesis of5-[(E)-4,7-diacetoxy-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxybutyl)-2-cyclopentenoneand5-[(E)-4,7-diacetoxy-2-heptenylidene]-4-acetoxy-2-methylthio-4-(4-phenoxybutyl)-2-cyclopentenone##STR256##

To a solution of 23 mg of5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxybutyl)-2-cyclopentenoneobtained in Example 91 dissolved in 2 ml of dichloromethane was added200 μl of triethylamine. Under ice-cooling and stirring. 20 μl ofacetylchloride was added, and the mixture was stirred at 0° C. for 2hours. Saturated aqueous sodium chloride was added, and the mixture wasextracted with ethyl acetate. The extract was dried over anhydroussodium sulfate, filtrate and concentrated, followed by silica gel columnchromatography to give 11 mg (yield 43%) of5-[(E)-4,7-diacetoxy-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxybutyl)-2-cyclopentenone(J) and 4 mg (yield 17%) of5-[(E)-4,7-diacetoxy-2-heptenylidene]-4-acetoxy-2-methylthio-4-(4-phenoxybutyl-2-cyclopentenone(K).

Spectrum data

¹ H-NMR CDCl₃ δ

(J) 1.1-2.1 (11H, m), 2.01 (3H, s), 2.13 (3H, s),

2.36 (3H, s), 3.6-4.5 (5H, m), 6.0-6.5

(1H, m), 6.69 (1H, s), 6.7-7.2 (4H, m),

7.2-7.5 (3H, m).

(K) 1.1-2.1 (10H, m), 2.01 (3H, s), 2.04 (3H, s),

2.13 (3H, s), 2.35 (3H, s), 3.6-4.5 (5H, m),

6.0-6.5 (1H, m), 6.64 (1H, s), 6.7-7.2 (4H, m)

7.2-7.5 (3H, m).

EXAMPLE 111 Synthesis of2-methylthio-5-(6-carboxyhexylidene)-4-hydroxy-4-octyl-2-cyclopentenone##STR257##

To a solution of 16 mg of2-methylthio-4-hydroxy-5-(6-methoxycarbonylhexylidene)-4-octyl-2-cyclopentenoneobtained in Example 101, dissolved in 1 ml of acetone, 11 ml of 0.1Mphosphate buffer of pH 8 was added. Under stirring, 1.5 mg of pig liveresterase was added, and the mixture was stirred at 30-35° C. for 130hours. After the mixture was adjusted to pH 4 with 0.1N hydrochloricacid, ammonium sulfate was added to saturation and the mixture wasfiltered with addition of ethyl acetate. The filtrate was extracted withethyl acetate, the organic layers were combined and washed withsaturated aqueous sodium chloride. After drying over anhydrous magnesiumsulfate, filtration and concentration, the concentrate was subjected tosilica gel column chromatography to give 7.7 mg (yield 47%) of2-methylthio-5-(6-carboxyhexylidene)-4-hydroxy-4-octyl-2-cyclopentenone.

Spectrum data

¹ H-NMR CDCl₃ δ

0.86 (3H, t, J=5.7 Hz), 1.1-2.2 (22H, m),

2.2-2.5 (2H, m), 2.36 (3H, s), 2.5-3.0

(2H, m), 6.5-6.9 (2H, m).

EXAMPLE 112 Evaluation of antitumor activity

Cancer cells were grown in an RPMI 1640 culture medium containing 10% offetal calf serum.

The compound to be tested was dissolved in 99.5% ethanol and was addedto the medium so that the final concentration of the ethanol was 0.1% orless. As a control, 0.1% ethanol was used. L1210 cancer cells wereinoculated at a concentration of 1×10⁵ cells/ml in the medium and weregrown for 4 days. The number of live cells was determined by trypan bluestaining.

The results are shown in Table 10.

                                      TABLE 10                                    __________________________________________________________________________    Compound to be tested                          IC.sub.50                      __________________________________________________________________________                                                   (μg/ml)                      ##STR258##                 2-methylthio-5-(6-methoxycarbonyl- hexylidene)                                -4-(3-hydroxy-1-octenyl)-2- cyclopentenone                                                       5.0                             ##STR259##                 2-methylsulfinyl-5-(6-methoxycarbonyl-                                        hexylidene)-4-(3-hydroxy-1-octenyl)-2-                                        cyclopentenone     4.0                             ##STR260##                 2-methylsulfinyl-5-[( .sub.--E)-4,7-dihydroxy-                                2- heptenylidene]-4-(4-phenoxybutyl)-4-                                       hydroxy-2-cyclopentenone                                                                         1.0                             ##STR261##                 2-methylsulfonyl-5-[( .sub.--E)-4,7-dihydroxy-                                2- heptenylidene]-4-(4-phenoxybutyl)-4-                                       hydroxy-2-cyclopentenone                                                                         2.0                             ##STR262##                 2-methylthio-5-[( .sub.--Z)-4,7-dihydroxy-2-                                  heptenylidene]-4-(4-phenoxybutyl)-4- hydroxy-2                                -cyclopentenone    1.2                             ##STR263##                 2-methylsulfinyl-5-[( .sub.--Z)-4,7-dihydroxy-                                2- heptenylidene]-4-(4-phenoxybutyl)-4-                                       hydroxy-2-cyclopentenone                                                                         1.0                             ##STR264##                 2-methylthio-5-[( .sub.--Z)-4,7-dihydroxy-2-                                  heptenylidene]-4-(4-phenoxybutylidene)-                                       2-cyclopentenone   3.5                             ##STR265##                 2-methylsulfinyl-5-[( .sub.--Z)-4,7-dihydroxy-                                2- heptenylidene]-4-(4-phenoxybutylidene)-                                    2-cyclopentenone   0.1                            __________________________________________________________________________

EXAMPLE 113 Determination (1) of bone formation activity

Human osteoblast (SAM-1, 12PDL) was cultured in α-MEM containing 10%fetal bovine serum, and when a stable growth was attained, apredetermined concentration of the compound was added in the presence of2 mM α-glycerophosphoric acid salt, followed by treatment for 25 days.The cell layer was washed with Hank's solution and the alkaliphosphatase activity then measured by absorption at OD₄₁₀. Next, calciumand phosphorus were extracted with a 5% perchloric acid solution andquantitated, and DNA was extracted with 5% perchloric acid at 90° C.,and the weight thereof quantitated. These evaluations were conductedaccording to the methods of Koshihara et al (Biochemical and BiophysicalResearch Communication Vol 145, No. 2, 1987, p. 651). The results areshown in Table 11.

                                      TABLE 11                                    __________________________________________________________________________    Measurement of alkali phosphatase (ALP), calcium (Ca),                        phosphorus (P) per DNA                                                                                          ALP                                                                           OD 410 nm/                                                                            Ca      P                           Compound                          μg DNA                                                                             μg/μg DNA                                                                       μg/μg                 __________________________________________________________________________                                                      DNA                         Control                           1.148 ± 0.050                                                                      0.386 ± 0.245                                                                      1.528 ± 0.316             ##STR266##                 10.sup.-7 M 10.sup.-6 M                                                             0.333 ± 0.039 p < 0.001 1.447 ±                                         0.268 p < 0.001                                                                       8.847 ± 1.485 p < 0.05                                                     29.410 ± 1.263 p                                                                   5.270 ± 0.144 p <                                                          0.001 15.743 ± 0.630                                                        < 0.01                     2-methylthio-5-[( .sub.--Z)-4,7-                                              dihydroxy-2-heptenylidene]-                                                   4-(4-phenoxybutyl)-4-                                                         hydroxy-2-cyclopentenone                                                      __________________________________________________________________________

EXAMPLE 114 Determination (2) of bone formation activity

Human osteoblast (KK-3, 18PDL) was cultured in α-MEM containing 10%fetal bovine serum, and when a stable growth was attained, apredetermined concentration of the compound was added in the presence of2 mM α-glycerophosphoric acid salt, followed by treatment for 14 days.The cell layer was washed with physiological salt solution and thealkali phosphatase activity then measured by absorption at OD₄₁₅. Then,calcium and phosphorus were extracted with a 2N hydrochloric acidsolution and quantitated. The results are shown in Table 12.

                                      TABLE 12                                    __________________________________________________________________________                                      ALP       Ca    P                           Compound                          OD 415 nm/dish                                                                          μg/dish                                                                          μg/dish                  __________________________________________________________________________    Control (No compound)             0.44 ± 0.12                                                                          106 ± 12                                                                         61 ± 10                   ##STR267##                 10.sup.-8 M 10.sup.-7 M 10.sup.-6                                                   0.28 ± 0.06 0.48 ± 0.08 1.12 ±                                       0.31       84 ± 10 111 ± 9 168                                                    ± 1                                                                              47 ± 6 63 ± 6 92                                                        ± 2                      2-methylthio-5-[( .sub.--Z)-4,7-                                              dihydroxy-2-heptenylidene]-                                                   4-(4-phenoxybutyl)-4-                                                         hydroxy-2-cyclopentenone                                                       ##STR268##                 10.sup.- 8 M 10.sup.-7 M 10.sup.-6                                                  0.24 ± 0.02 0.56 ± 0.08 0.97 ±                                       0.07       87 ± 6 114 ± 4 168                                                     ± 9                                                                              47 ± 2 64 ± 3 93                                                        ± 4                      2-methylthio-5-[( .sub.--E)-4,7-                                              dihydroxy-2-heptenylidene]-                                                   4-(4-phenoxybutyl)-4-                                                         hydroxy-2-cyclopentenone                                                      __________________________________________________________________________

EXAMPLE 115 Determination (3) of bone formation activity

Human osteoblast (KK-3, 18PDL) was cultured in α-MEM containing 10%fetal bovine serum, and when a stable growth was attained, apredetermined concentration of the compound was added in the presence of2 mM α-glycerophosphoric acid salt, followed by treatment for 14 days.The cell layer was washed with a physioligical salt solution and thealkali phosphatase activity then measured by absorption at OD₄₁₅. Next,calcium and phosphorus were extracted with a 2N hydrochloric acidsolution and quantitated.

The results are shown in Table 13.

                                      TABLE 13                                    __________________________________________________________________________                                       ALP       Ca    P                          Compound                           OD 415 nm/dish                                                                          μg/dish                                                                          μg/dish                 __________________________________________________________________________    Control (No compound)              0.72 ± 0.17                                                                           90 ± 8                                                                          51 ± 5                   ##STR269##                  10.sup.-7 M 10.sup.-6 M                                                             0.69 ± 0.02 0.75 ± 0.17                                                           110 ± 30 105 ±                                                                60 ± 14 57 ± 1       2-methylthio-5-[( .sub.--Z)-4,7-                                              dihydroxy-2-heptenylidene]-                                                   4-(4-phenoxybutylidene)-2-                                                    cyclopentenone                                                                 ##STR270##                  10.sup.-7 M 10.sup.-6 M                                                             0.81 ± 0.11 0.92 ±                                                                 89 ± 1 109                                                                      52 ± 1 61 ± 4        2-methylsulfinyl-5-[(Z)-4,7-                                                  dihydroxy-2-heptenylidene]-                                                   4-(4-phenoxybutylidene)-4-                                                    hydroxy-2-cyclopentenone                                                       ##STR271##                  10.sup.-7 M 10.sup.-6 M                                                             0.94 ± 0.07 0.94 ± 0.11                                                            85 ± 10 109 ±                                                                48 ± 4 60 ± 0.5      2-methylsulfonyl-5-[( .sub.--Z)-4,7-                                          dihydroxy-2-heptenylidene]-                                                   4-(4-phenoxybutylidene)-2-                                                    cyclopentenone                                                                 ##STR272##                  10.sup.-7 M 10.sup.-6 M                                                             0.73 ± 0.02 0.68 ± 0.10                                                            78 ± 4  79                                                                      46 ± 2 43 ± 4        2-methylthio-5-(6-methoxy-                                                    carbonylhexlidene)-4-(3-                                                      hydroxy-1-octenyl)-2-cyclo-                                                   pentenone                                                                     __________________________________________________________________________

We claim:
 1. A 2-substituted-2-cyclopentenone represented by the formula(I): ##STR273## wherein A is a hydroxyl group or ##STR274## and B is ahydrogen atom or A and B are absent and a double bond is present betweenthe two carbon atoms to which A and B would be bound;R¹ represents analkyl group having 1 to 10 carbon atoms, an aralkyl group having 7 to 10carbon atoms, or an aryl group having 6 to 10 carbon atoms or saidalkyl, aralkyl or aryl group substituted with a hydroxyl group, a tri(C₁-C₇)hydrocarbonsilyloxy group, a halogen atom, an alkoxy group, anacyloxy group, an acyl group, an alkoxycarbonyl group, or a carboxylgroup; R² represents an aliphatic hydrocarbon group having from 1 to 10carbon atoms or an aliphatic hydrocarbon group having from 1 to 10carbon atoms substituted with --COOR⁵, wherein R⁵ represents a hydrogenatom, an alkyl group having 1 to 10 carbon atoms or one equivalentcation; --OR⁶, wherein R⁶ represents a hydrogen atom, an acyl grouphaving 2 to 7 carbon atoms, a tri(C₁ -C₇)hydrocarbonsilyloxy group, amethoxymethyl group, a 1-ethoxyethyl group, a 2-methoxy-2-propyl group,a 2-ethoxy-2-propyl group, a 2-methoxyethoxy-methyl group, atetrahydropyran-2-yl group, a tetrahydrofuran-2-yl group, a6,6-dimethyl-3-oxa-2-oxo-bicyclo[3.1.0]-hexan-4-yl group, an aromatichydrocarbon group which may be substituted with a halogen atom, ahydroxyl group, a tri(C₁ -C₇)hydrocarbonsilyloxy group, a carboxylgroup, an acyloxy group having 2 to 7 carbon atoms, an acyl group having2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms,an alkyl group having 1 to 4 carbon atoms, or an alkoxy group having 1to 4 carbon atoms; an aromatic hydrocarbon group which may besubstituted with a halogen atom, a hydroxyl group, a tri(C₁-C₇)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, analkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1to 4 carbon atoms, or an alkoxy group having 1 to 4 carbon atoms; or analicyclic group which may be substituted with a halogen atom, a hydroxylgroup, a tri(C₁ -C₇)hydrocarbonsilyloxy group, a carboxyl group, anacyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, analkyl group having 1 to 4 carbon atoms, or an alkoxy group having 1 to 4carbon atoms; R³ represents an aliphatic hydrocarbon group having from 1to 10 carbon atoms or an aliphatic hydrocarbon group having from 1 to 10carbon atoms substituted with --COOR⁵, wherein R⁵ represents a hydrogenatom, an alkyl group having 1 to 10 carbon atoms or one equivalentcation; --OR⁶, wherein R⁶ represents a hydrogen atom, an acyl grouphaving 2 to 7 carbon atoms, a tri(C₁ -C₇)hydrocarbonsilyloxy group, amethoxymethyl group, a 1-ethoxyethyl group, a 2-methoxy-2-propyl group,a 2-ethoxy-2-propyl group, a 2-methoxyethoxy-methyl group, atetrahydropyran-2-yl group, a tetrahydrofuran-2-yl group, a6,6-dimethyl-3-oxa-2-oxo-bicyclo[3.1.0]-hexan-4-yl group, an aromatichydrocarbon group which may be substituted with a halogen atom, ahydroxyl group, a tri(C₁ -C₇)hydrocarbonsilyloxy group, a carboxylgroup, an acyloxy group having 2 to 7 carbon atoms, an acyl group having2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms,an alkyl group having 1 to 4 carbon atoms, or an alkoxy group having 1to 4 carbon atoms; an aromatic hydrocarbon group which may besubstituted with a halogen atom, a hydroxyl group, a tri(C₁-C₇)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, analkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1to 4 carbon atoms, or an alkoxy group having 1 to 4 carbon atoms; or analicyclic group which may be substituted with a halogen atom, a hydroxylgroup, a tri(C₁ -C₇)hydrocarbonsilyloxy group, a carboxyl group, anacyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, analkyl group having 1 to 4 carbon atoms, or an alkoxy group having 1 to 4carbon atoms; wherein R³ is attached via a single bond, and X representsa hydrogen atom, a hydroxyl group, an alkoxy group, a tri(C₁-C₇)hydro-carbonsilyloxy group, an acetal group selected from the groupconsisting of a methoxymethoxy group, a 1-ethoxyethoxy group, a2-methoxyethoxymethoxy group, and a tetrahydropyran-2-yloxy group or anacyloxy group or R³ is attached via a double bond and X is absent; and mand n represent 0, 1 or
 2. 2. A 2-substituted-2-cyclopentenone asclaimed in claim 1 represented by the formula (I-a): ##STR275## whereinR¹, R², R³, X and n are as defined in claim 1; and the representationrepresents that the substituent bonded to the double bond is in anE-arrangement or a Z-arrangement or a mixture thereof at any desiredratio.
 3. A 2-substituted-2-cyclopentenone as claimed in claim 1represented by the formula (I-b): ##STR276## wherein A¹ is a hydroxylgroup or ##STR277## R¹, R², R³, X, m and n are the same as defined inclaim
 1. 4. A 2-substituted-2-cyclopentenone as claimed in claim 1represented by the formula (I-a-1): ##STR278## wherein R¹, R², n are asdefined in claim 1, the representation represents that the substituentbonded to the double bond is in an E-arrangement or a Z-arrangement or amixture thereof at any desired ratio and R³⁴ has the same meaning as R².5. A 2-substituted-2-cyclopentenone as claimed in claim 1 represented bythe formula (I-a-2): ##STR279## wherein R¹, R², and n are as defined inclaim 1, R³⁴ has the same meaning as R², and the representationrepresents that the substituent bonded to the double bond is in anE-arrangement or a Z-arrangement or a mixture thereof at any desiredratio;R⁴ represents a hydrogen atom, an alkyl group having 1 to 3 carbonatoms, a tri(C₁ -C₇)hydrocarbonsilyl group, a methoxymethyl group, a1-ethoxy ethyl group, a 2-methoxyethoxymethyl group, atetrahydropyran-2-yl group, or an acyl group having 1 to 4 carbon atoms.6. A 2-substituted-2-cyclopentenone as claimed in claim 1 represented bythe formula (I-a-3'): ##STR280## wherein R¹, R² and n are as defined inclaim 1, the representation represents that the substituent bonded tothe double bond is in an E-arrangement or a Z-arrangement or a mixturethereof at any desired ratio; andR³³ represents a hydrogen atom, analiphatic hydrocarbon group having from 1 to 9 carbon atoms or analiphatic hydrocarbon group having from 1-9 carbon atoms substitutedwith --COOR⁵, where R⁵ represents a hydrogen atom, an alkyl group having1 to 10 carbon atoms or one equivalent cation; --OR⁶, where R⁶ is anacyl group having 2 to 7 carbon atoms, a tri(C₁ -C₇)hydrocarbonsilyloxygroup, a methoxymethyl group, a 1-ethoxyethyl group, a2-methoxy-2-propyl group, a 2-ethoxy-2-propyl group, a2-methoxyethoxy-methyl group, a tetrahydropyran-2-yl group, atetrahydrofuran-2-yl group, a6,6-dimethyl-3-oxa-2-oxo-bicyclo[3.1.0]-hexan-4-yl group, an aromatichydrocarbon group which may be substituted with a halogen atom, ahydroxyl group, a tri(C₁ -C₇)hydrocarbonsilyloxy group, a carboxylgroup, an acyloxy group having 2 to 7 carbon atoms, an acyl group having2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms,an alkyl group having 1 to 4 carbon atoms, or an alkoxy group having 1to 4 carbon atoms; an aromatic hydrocarbon group which may besubstituted with a halogen atom, a hydroxyl group, a tri(C₁-C₇)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, analkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1to 4 carbon atoms, or an alkoxy group having 1 to 4 carbon atoms; or analicyclic group which may be substituted with a halogen atom, a hydroxylgroup, a tri(C₁ -C₇)hydrocarbonsilyloxy group, a carboxyl group, anacyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, analkyl group having 1 to 4 carbon atoms, or an alkoxy group having 1 to 4carbon atoms.
 7. A 2-substituted-2-cyclopentenone as claimed in claim 1represented by the formula (I-b-1): ##STR281## wherein A¹ is a hydroxylgroup or ##STR282## wherein m represents 0, 1 or 2, R¹, R² and n are asdefined in claim 1, and R³⁴ has the same meaning as R². 8.2-substituted-2-cyclopentenone as claimed in claim 7 wherein A¹ is ahydroxyl group.
 9. 2-substituted-cyclopentenone as claimed in claim 1represented by the formula (I-b-2): ##STR283## wherein R¹, R² and n areas defined in claim 1, R³⁴ has the same meaning as R², and R⁴ representsa hydrogen atom, an alkyl group having 1 to 3 carbon atoms, a tri(C₁-C₇)hydrocarbonsilyl group, a methoxymethyl group, a 1-ethoxy ethylgroup, a 2-methoxyethoxymethyl group, a tetrahydropyran-2-yl group, oran acyl group having 1 to 4 carbon atoms. 10.2-substituted-2-cyclopentenone as claimed in claim 1, wherein R¹ is asubstituted or unsubstituted alkyl group having 1 to 5 carbon atoms. 11.2-substituted-cyclopentenone as claimed in claim 1, wherein R¹ ismethyl.
 12. 2-substituted-2-cyclopentenone as claimed in claim 1,wherein the substituent on R² is a methoxycarbonyl group, a hydroxylgroup, an acetoxy group or a t-butyldimethylsilyloxy group. 13.2-substituted-2-cyclopentenone as claimed in claim 1, wherein thesubstituents when R³ is substituted are a phenoxy group, a hydroxygroup, a tetrahydropyran-2-yloxy group, or a t-butyldimethylsilyloxygroup.
 14. 2-substituted-2-cyclopentenone as claimed in claim 1, whereinX is a hydroxyl group, a methoxy group, an acetoxy group or atrimethylsilyloxy group.
 15. 2-substituted-2-cyclopentenone as claimedin claim 1, wherein X is a hydrogen atom, a hydroxyl group, a methoxygroup, an ethoxy group, a trimethylsilyloxy group, or an acetoxy group.16. An antitumor agent containing, as an essential component, at leastone 2-substituted-2-cyclopentenone of claim 1 and a pharmaceuticallyacceptable carrier or excipient.
 17. A bone formation acceleratorcontaining, as an essential component, at least one2-substituted-2-cyclopentenone of claim 1 and a pharmaceuticallyacceptable carrier or excipient.